National Cancer Institute

U.S. DEPARTMENT 

OF HEALTH AND 

HUMAN SERVICES

National Institutes 

of Health

A report published by the Office of Cancer 

Complementary and Alternative Medicine

 NCI’s Annual Report on 

Complementary

 and Alternative 

 Medicine:

 Fiscal Year 2005

Since the National Cancer Act of 1971, we have made tremendous strides in the fight 

against cancer. Today, that progress is evidenced by more than 10.5 million cancer survivors in 

the United States, and more people are living longer with cancer than ever before. Thanks to 

the groundbreaking work of the cancer research community, the future holds much promise 

for eliminating the suffering and death due to cancer in the years to come. One aspect of the 

research agenda that will be critical to our efforts is complementary and alternative medicine 

(CAM) and the potential that this area of medicine has for the prevention, diagnosis, and 

treatment of cancer, cancer-related symptoms, and side effects of conventional treatment.

In recent years, the National Cancer Institute (NCI) has responded to the therapeutic 

potential of CAM by making a significant investment in the scientific evaluation of and 

communication about CAM therapies for cancer. In fact, this report NCI’s Annual Report on 

Complmentary and Alternative Medicine: Fiscal Year 2005 outlines NCI’s many accomplishments in the growing field of CAM.

I am encouraged and enthusiastic about what NCI has accomplished in advancing the 

evidence-base of CAM and what each of those achievements means for the future. I applaud 

the work of our NCI scientists and the many extramural researchers who we support through 

our various programs. Likewise, I value the contributions of our numerous domestic and 

international partners. 

I hope you find this report to be helpful in outlining our scientific, training, and communication accomplishments in the past year. I also hope that the report will generate increased 

dialogue about CAM—especially between patients and their health care professionals—and 

its appropriate use in conjunction with conventional medicine. Cancer patients and survivors 

want and deserve to have credible, unbiased information about any treatment or compound 

that they are considering as part of their medical regimen and healthy lifestyle choices.

This annual report was commissioned to convey the breadth and depth of NCI’s CAM 

activities, share the commitment of the cancer research community that I witness every day, 

and express the sense of hope that progress brings as we seek to eliminate suffering and death 

due to cancer.

Thank you for your consideration.

Mark Clanton, M.D.

Deputy Director and Deputy Director for Cancer Care Delivery Systems

National Cancer Institute

NCI’s Prospective Agenda for 

Complementary and Alternative Medicine

DIRECTOR’S MESSAGE


NCI CAM Annual Report 2005

Table of Contents

Director’s Message ������������������������������������������������������������������������������������������������������1

Introduction ����������������������������������������������������������������������������������������������������������������4

PART I: Office of Cancer Complementary and Alternative Medicine�������������������7

PART II: NCI CAM Communications Programs���������������������������������������������������� 11

PART III: Training and Conferences ���������������������������������������������������������������������� 15

PART IV: NCI Research in Complementary and Alternative Medicine ��������� 19

NCI CAM Research Portfolio Analysis������������������������������������������������������� 20

NCI Grant Support: The Gift That Keeps on Giving������������������������������������ 23

Major Accomplishments in 2005 ������������������������������������������������������������ 24

Low-Fat Diet May Lower Risk of Breast Cancer Recurrence 25

WHEL Study Testing High Vegetable Diet for Breast Cancer Recurrence 26

Intensive Lifestyle Changes Show Benefits for Prostate Cancer 28

Addressing NCI’s Strategic Areas �������������������������������������������������������������������������� 29

Understanding the Causes and Mechanisms of Cancer���������������������������������������� 30

Milk Thistle and Prostate Cancer: Moving from Bench to Bedside 31

Selenium and Cancer Prevention: Investigating Mechanisms of Anti-angiogenesis 32

Accelerating Progress in Cancer Prevention���������������������������������������������������������� 33

Fish Diet May Have Role in Preventing Prostate Cancer 34

Preventive Role of Soy Food in Endometrial Cancer Explored in Chinese Study 36

Prevention of Esophageal Cancer with Berries 37

Chinese Herbal Agents Tested in Lung Cancer Prevention 38

Physicians Health Study II: Prevention Trial of Vitamins 40
Table of Contents

Developing Effective and Efficient Treatments������������������������������������������������������41

Folate Depletion and Cancer Cell Resistance to Cisplatin 42

Scientists Study Response to Multivitamins/Minerals During Cancer Therapy 43

Meditation May Enhance Immune System for Breast Cancer Patients 44

Whole-Body Hyperthermia (Fever) May Help Tumor Control 46

Testing the Effects of Vitamin D on Prostate Cancer in Mice 47

Chinese Herbal Extract Shows Promise for Treating Immune Disorders 48

Improving the Quality of Cancer Care �������������������������������������������������������������������49

Stress Management and the Immune Response in Breast Cancer Patients 50

Complementary and Alternative “Comfort Care” at the End of Life 52

Massage May Enhance Quality of Life in Stem Cell Transplant Patients 53

Improving the Quality of Life for Cancer Patients,

Survivors, and Their Families����������������������������������������������������������������������������������54

Acupressure Used to Treat Nausea From Chemotherapy 55

Foot Reflexology May Enhance Quality of Life in Breast Cancer Patients 56

Hypnotherapy Eases Hot Flashes in Breast Cancer Survivors 57

Overcoming Cancer Health Disparities�����������������������������������������������������������������58

CAM Survey of California Consumers Includes Underserved Minority Groups 59

NCI Scientists Spearhead Pioneering Research on CAM ������������������������������������60

Testing Traditional Chinese Medicines for Anti-Cancer Agents 61

Plant Compounds Protect Cells from Carcinogen-Induced Damage 62

Impact of Legume (Dry Beans) Diet on Colorectal Cancer Risk Studied 64

NCI’s Nutritional Epidemiology Branch Focuses on

Impact of Diet and Activity on Cancer Risk 66

Selenium Studied for Prevention of Esophageal and Gastric Cancers 67

Preventive Study of Gastric Cancer Emerges from Collaboration with China 68

Lessons from China Could Enhance Prostate Cancer Prevention in the West 69

Scientific Publications ���������������������������������������������������������������������������������������������70

Appendix��������������������������������������������������������������������������������������������������������������������72

Organizational Chart ���������������������������������������������������������������������������������������������80


A. Alternative Medical Systems (and some specific 

components)

Definition: Alternative medical systems are built upon 

complete systems of theory and practice. Often, these 

systems have evolved apart from and earlier than the 

conventional medical approach used in the United 

States.

Examples: Acupuncture, Ayurveda, Homeopathy, 

Naturopathy, Traditional Chinese Medicine, Tibetan 

Medicine 

B. Energy Therapies 

Definition: Energy therapies involve the use of energy 

fields. They are of two types: 

1. Biofield therapies are intended to affect energy 

fields that purportedly surround and penetrate the 

human body. The existence of such fields has not yet 

been scientifically proven.

Examples: Qi gong, Reiki, Therapeutic touch 

2. Electromagnetic-based therapies involve the unconventional use of electromagnetic fields, such as pulsed 

fields, magnetic fields, or alternating current or direct 

current fields. 

Examples: pulsed electromagnetic fields, magnet 

therapy 

C. Exercise Therapies 

Examples: T’ai chi, yoga asanas 

D. Manipulative and

Body-Based Methods 

Definition: Manipulative and body-based methods in 

CAM are based on manipulation and/or movement of 

one or more parts of the body. 

Examples: Chiropractic, therapeutic massage, 

osteopathy, reflexology

E. Mind-body Interventions 

Definition: A variety of techniques designed to 

enhance the mind’s capacity to affect bodily function 

and symptoms. 

Examples: meditation, hypnosis, art therapy, biofeedback, mental healing, imagery, relaxation therapy, 

support groups, stress management, music therapy, 

cognitive-behavioral therapy, dance therapy, aromatherapy. 

F. Nutritional Therapeutics 

Definition: An assortment of nutrients and non-nutrients, bioactive food components that are used as 

chemo-preventive agents, and the use of specific 

foods or diets as cancer prevention or treatment 

strategies. 

Examples: dietary regimens such as macrobiotics, 

vegetarian, Gerson diet, Kelley/Gonzalez regimen; 

vitamins, dietary macronutrients, dietary supplements, 

soy phytoestrogens, nutrient minerals and elements 

(amino acids), antioxidants, glutamine, selenium, 

coenzyme Q10, orthomolecular medicine. 

G. Pharmacological and biologic treatments 

Definition: Off-label use of prescription drugs, hormones, complex natural products, vaccines, and other 

biological interventions not yet accepted in mainstream 

medicine. 

Examples: Antineoplastons, products from honey bees, 

mistletoe, shark cartilage, 714X, low dose naltrexone, 

metenkephalin, immunoaugmentative therapy, laetrile, 

hydrazine sulfate, melatonin. 

Sub-category: Complex Natural Products

Definition: An assortment of plant samples (botanicals), extracts of crude natural substances, and unfractionated extracts from marine organisms used for 

healing and treatment of disease. 

Examples: herbs and herbal extracts, mixtures of tea 

polyphenols, shark cartilage 

H. Spiritual Therapies 

Examples: Intercessory prayer, spiritual healing 

Figure 1. Major Categories of CAM Therapies
CAM is often defined as any medical system, 

practice, or product that is not thought of as “western 

medicine” or standard medical care. Complementary

medicine means it is used along with standard medicine, also called conventional medicine. Alternative

medicine is used in place of standard treatments. 

CAM treatments may include dietary supplements, 

megadose vitamins, herbal preparations, special teas, 

acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. (See Figure 1, opposite 

page for the major categories of CAM therapies.) 

NCI has a long history of involvement in the 

scientific evaluation of CAM treatments for cancer. 

From the 1940s through the 1970s, NCI assessed 

information about practices then in use by cancer 

patients such as the Gerson regimen, Hoxsey, and 

the use of laetrile. In 1991, the NCI Best Case Series 

Program was established to formalize the evaluation 

of case reports of potential new cancer treatments 

from CAM domains. Examples of topics that came 

through the early years of this program include antineoplastons and the Kelly/Gonzalez Regimen. 

In Fiscal Year (FY) 2005, NCI’s research expenditures for CAM is an estimated $121,076,919 for 

the funding of over 400 CAM research projects. 

The projects in this diverse portfolio are managed by 

program staff from each of the Institute’s extramural 

grant funding divisions (Division of Cancer Biology, 

Division of Cancer Control and Population Sciences, Division of Cancer Prevention, and Division 

of Cancer Treatment and Diagnosis),and principal 

investigators from the intramural components (Center for Cancer Research and Division of Cancer 

Epidemiology and Genetics).

As this Annual Report on CAM in cancer indicates, NCI is committed to an integrated approach to 

marshalling all of the many resources and approaches 

necessary to make cancer a condition that is—at 

worst—a manageable, chronic illness similar to most 

heart disease and diabetes. We believe that evidencebased CAM techniques, systems, and products can 

have an important role in helping us reach that 

worthwhile goal.

T h e N a t i o n a l C a n c e r I n s t i t u t e ’s ( N C I ) O f f i c e o f C a n c e r

Complementary and Alternative Medicine (OCCAM) is proud to present this 

first NCI’s Annual Report on Complementary and Alternative Medicine: Fiscal 

Year 2005. This unique report provides a closer look at NCI’s comprehensive and 

exciting research portfolio into complementary and alternative medicine (CAM) 

approaches for cancer.

Introduction

Introduction

PART I

Office of Cancer Complementary

and Alternative Medicine
NCI CAM Annual Report 2005

NCI’s Office of Cancer Complementary and 

Alternative Medicine (OCCAM) is largely responsible for overseeing the Institute’s growing research 

agenda in CAM related to cancer prevention, 

diagnosis, treatment, symptom management, and 

rehabilitation. Established in October 1998 and 

directed by medical oncologist Jeffrey D. White, 

M.D., OCCAM also acts as NCI’s link to the public, the CAM community, and cancer researchers 

regarding CAM and cancer. Additionally, OCCAM 

collaborates with other governmental and nongovernmental organizations such as the National Center for Complementary and Alternative Medicine 

(NCCAM) and patient advocacy groups, on cancer 

CAM issues.

OCCAM has been building bridges between 

CAM practitioners and the cancer research community by creating funding opportunities to investigate CAM approaches using scientifically rigorous research methods, working with other NCI 

Divisions and Centers to facilitate the testing of 

CAM approaches to cancer management, and helping CAM researchers overcome the challenges 

unique to CAM approaches and those associated 

with the grant application process. 

Research Development and Support

Program | Through its Research Development 

and Support Program (RDSP), OCCAM has 

expanded the funding opportunities for research 

in cancer CAM. RDSP staff assist investigators 

in identifying funding opportunities and provide 

assistance in the pre- and post-review periods of 

grant application. In addition, RDSP Director 

Wendy Smith, Ph.D., coordinates programs and 

initiatives designed to stimulate research in cancer 

CAM as well as activities to develop the foundation 

of the science in cancer CAM research. 

RDSP activities have also included the establishment of an expert panel in cancer CAM research, 

an invited speaker series, and a workshop to assist 

investigators in preparing grant applications in 

cancer CAM. 

Awarding NCI’s first grant to 

develop an international center of 

cancer CAM research (page 9)

Hosting the fourth Invited Speaker 

Series lecture (page 17)

Providing supplemental grant 

support to members of the Community Clinical Oncology Program 

(including Wake Forest University) 

(page 23)

ß

ß

ß

Presenting at the Best/Worst 

Case-International Workshop in 

Tromsø, Norway (See NCI CAM 

News Winter 2006 issue for more 

information.) 

Collaborating with other federal 

groups to produce Thinking About 

Complementary and Alternative 

Medicine, a patient and family 

education booklet (page 13)

ß

ß

Preparing for the first Practice 

Outcomes Monitoring and 

Evaluation Systems project in 

Calcutta, India (page 10)

Supplying programmatic support 

for Society for Integrative 

Oncology’s 1st International 

Conference (page 17)

ß

ß

Reviewing cases submitted to the 

NCI Best Case Series Program 

(page 9)

Organizing and leading a cancer 

CAM grant writing workshop 

(page 16)

ß

ß

Examples of OCCAM Activities in FY 2005 

NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM) 

is largely responsible for overseeing the Institute’s growing research agenda in 

CAM related to cancer prevention, diagnosis, treatment, symptom management, 

and rehabilitation.


Comm u nications and O u treach

Program | OCCAM’s Communications and 

Outreach Program, coordinated by Shea Buckman, 

M.A., develops and disseminates information about 

NCI program initiatives and funding opportunities, 

workshops and other events, and educational materials through OCCAM’s Web site and publications.

 This program also assesses the opinions, interests, and informational needs of cancer researchers, 

CAM practitioners, and cancer patients regarding CAM research via surveys and focus groups. 

Results from these explorations are used to guide 

outreach efforts to these communities.

Practice Assessment Program | 

OCCAM’s Practice Assessment Program, 

coordinated by Commander (U.S. Public Health 

Service) Colleen Lee, R.N., M.S., reviews 

retrospective and prospective data on cancer patients 

treated with alternative therapies. The best known 

component of the Practice Assessment Program 

is the NCI Best Case Series Program, which 

provides an opportunity for CAM practitioners to 

submit medical data regarding their cancer CAM 

treatments. 

Practitioners are asked to submit patient records 

for evaluation by experts in clinical assessment and 

cancer treatment research. Results of the NCI Best 

Case Series Program include recommendation for 

NCI-initiated research and the sharing of well-documented best cases with interested members of the 

scientific community in order to stimulate research. 

NCI Best Case Series Program Highlights

Since OCCAM’s creation in 1998, its staff has 

worked with CAM practitioners to identify appropriate, well-documented cases for inclusion in the 

In FY 2005, “Developmental Projects in 

Complementary Approaches to Cancer Care” 

(PA-04-053), a reissued program announcement (PA) originally initiated by RDSP, awarded 

9 grants. (See Figure 2 on page 10 for the 

number of cancer CAM grants awarded as a 

result of NCI funding announcements.) This 

PA was released to encourage and support the 

development of basic and clinical complementary cancer research. Funding for exploratory/

developmental projects through these R21 

grants is intended to provide the basis for more 

extended research studies by establishing the 

methodological feasibility, allowing the collection of data, and strengthening the scientific 

rationale for future grant applications. This 

announcement is also intended to attract the 

entry of promising investigators into research of 

these topics.

Through the R21 grant mechanism, 

OCCAM has awarded funding support for 

the development of NCI’s first international 

center that focuses on cancer CAM 

research. Originally awarded in FY 2003 

and active through FY 2005, this grant has 

allowed the establishment of a partnership 

between The University of Texas M. D. 

Anderson Cancer Center (MDACC) and 

the Cancer Hospital, Fudan University 

(CHFU) in Shanghai, China to investigate the 

potential benefits of some traditional Chinese 

medicine therapies for cancer patients. 

During the two-year pilot study, the 

International Center for Traditional Chinese 

Medicine has studied three aspects of 

traditional Chinese medicine: herbal and 

natural treatments that target the disease 

and related symptoms; acupuncture for 

the management of some side effects of 

cancer treatment; and the bio-behavioral 

effects of qigong and other mind/body-based 

interventions. The principle investigator of 

this grant Dr. Lorenzo Cohen has applied for 

and been awarded a four year U19* grant 

to continue and expand on the projects that 

started as a result of the R21. 

NCI’s First Grant to Develop an International Center of Cancer CAM Research 

*The R21 and U19 grants awarded to Dr. Cohen were in response to NCCAM funding announcements RFA-AT-03-002 and NOT-AT-04-008.

Office of Cancer Complementary and Alternative Medicine


NCI CAM Annual Report 2005

NCI Best Case Series (BCS) Program. Of those 

therapies that have been submitted, the following 

have completed the NCI BCS Program review and 

been found to warrant NCI-initiated research: 

Homeopathic therapy of cancer as practiced by 

Prasanta Banerji, D.Ht., (P. Banerji Homeopathic Research Foundation, Calcutta, India)

Insulin Potentiation Therapy as practiced by 

Steven G. Ayre, M.D., (Burr Ridge, Illinois) and 

Ross Hauser, M.D., (Oak Park, Illinois).

Macrobiotic Lifestyle Modification as taught by 

the Kushi Institute (Becket, Massachusetts)

In FY 2005, OCCAM prepared a broad agency 

announcement (N01-CO-57035-48), for release 

in FY 2006, to solicit contract proposals to perform research on the above mentioned therapies. A 

contract awarded as a result of this announcement 

would provide support for prospective research: 

pre-clinical, clinical trial, or both. http://www.cancer.gov/cam/research_funding_baa.html

POMES

Practice Outcomes Monitoring and Evaluation 

System (POMES) is a process for monitoring the 

outcomes in a small population of patients treated 

with an unconventional intervention as it is ordinarily administered, without altering the regimen’s 

delivery or outcome. The goal of a POMES project 

is to determine whether a phenomena observed in 

a retrospective case review can be seen with prospective observation of a larger population. Results 

from a POMES project can be used to justify an 

NCI-initiated clinical trial. 

•

•

•

In FY 2005, OCCAM staff initiated the start 

up of the first POMES project, titled “Homeopathic 

treatment of lung cancer patients at the P. Banerji 

Homeopathic Research Foundation (PBHRF) in 

Calcutta, India”. PBHRF had previously presented 

NCI with a case series of cancer patients treated 

with a unique homeopathic approach, in which two 

patients had sustained radiographic responses of 

pathologically confirmed lung cancers (one complete remission, one partial remission). In addition, 

PBHRF also presented records of two patients with 

pathologically confirmed esophageal cancers: one 

of which had a radiographic partial remission, one 

stable disease, and both of whom reportedly had 

complete resolution of related symptoms. These 

patients reportedly had received only the homeopathic preparations prescribed at the clinic. 

OCCAM’s review of these cases submitted by 

PBHRF lead to the development of a protocol for 

an observational study which would seek to provide 

an independent, prospective documentation and 

assessment of the outcomes that occur in 30–45 new 

lung cancer patients treated in the PBHRF clinic. 

The goal of this study is to estimate the frequency 

with which such responses occur and to thoroughly 

document all therapies received by these patients. 

If responses are documented in patients receiving 

only the homeopathic medications, the data from 

this study will be used to support the rationale for, 

and the design of pre-clinical and clinical studies to 

further explore this phenomenon.

Figure 2. Cancer CAM-Related Grants Awarded in FY 05 by Program 

Announcement (PA) and Request for Applications (RFA)

CA01-020 1 CA03-016 1 PA01-187 1 PA04-099 1 PAR03-009 1 AT01-002 1

CA02-007 2 CA03-018 1 PA02-001 2 PA96-008 2 PAR03-010 4 AT03-002 2

CA02-008 2 CA04-001 1 PA02-040 1 PA99-081 1 PAR03-153 6 OD03-008 1

CA02-009 2 CA04-002 1 PA02-124 1 PA99-163 1 PAR03-176 3 ES02-009 1

CA03-001 3 CA04-004 7 PA02-169 1 PAR00-025 9 PAR04-011 1 HS01-005 1

CA03-003 8 CA98-012 1 PA04-041 1 PAR01-110 1 PAR04-147 6 UNSOLICITED 196

CA03-004 3 CA99-003 2 PA03-169 1 PAR02-037 2 PAR04-155 1 TOTAL 351

CA03-006 1 PA00-080 1 PA04-034 1 PAR02-040 41 PAR99-167 2

CA03-007 1 PA01-015 1 PA04-053 9 PAR02-176 8 PAS02-009 2

10
PART II

NCI CAM

Communications Programs
NCI CAM Annual Report 2005

Providing Information Online | 

OCCAM’s Web site serves as NCI’s information 

hub on CAM issues at http://www.cancer.gov/

cam. It provides a wealth of information and 

timely updates about the Institute’s CAM research 

portfolio, grant opportunities, and other news. The site 

includes links to NCI-produced summaries—called 

Physician Data Query (PDQ®) summaries—about 

certain CAM therapies as well as shorter question 

and answer documents (Fact Sheets) about some 

treatments. During FY 2005, NCI released 4 PDQ 

summaries for health professionals for the following 

CAM therapies, bringing the total number of these 

summaries to 16. 

Acupuncture (http://www.cancer.gov/cancertopics/pdq/cam/acupuncture)

Aromatherapy (http://www.cancer.gov/cancertopics/pdq/cam/aromatherapy)

Gonzalez Regimen (http://www.cancer.gov/cancertopics/pdq/cam/gonzalez)

Milk Thistle (http://www.cancer.gov/cancertopics/pdq/cam/milkthistle)

•

•

•

•

In addition, health professional versions of the 

PDQ CAM summaries were converted into question-and-answer format summaries for patients in 

FY 2005. Fourteen such patient summaries are now 

available online. 

Online access is also provided to NCI’s PDQ 

Cancer Clinical Trials Registry. This registry currently includes approximately 4,500 abstracts of 

protocols that are open and approved to accept 

patients, including clinical studies on CAM 

approaches for cancer. To search for cancer CAM 

clinical trials, please visit http://www.cancer.gov/

cam/clinicaltrials_pdq.html. 

The PDQ database is used by health professionals and patients alike and may be searched a number 

of ways including by diagnosis, treatment modality, 

locality, or a combination of these search criteria.

Note: NCI’s Web sites do not offer personalized medical advice to individuals about their 

condition or treatment, and the resources on the 

sites should not be used as a substitute for professional medical care.

NCI directs communications programs that are committed to providing current 

and credible information resources about CAM to its stakeholders.

12
Producing Publications | In addition to the 

OCCAM Web site, various offices within NCI provide educational materials to health professionals and 

consumers in print format, including the informative 

booklet on Thinking About Complementary and Alternative Medicine, published in conjunction with the 

National Center for Complementary and Alternative Medicine (NCCAM). The 16-page publication 

was released in May 2005 and can be downloaded 

online at http://www.cancer.gov/cancertopics/

thinking-about-CAM, or ordered as a print copy 

from NCI’s Cancer Information Service (Inventory 

Number P042) by calling 1-800-4-CANCER (1-

800-422-6237) or from NCI’s Publications Locator 

at www.cancer.gov/publications.

Responding to Cancer CAM Inquiries | 

NCI’s Cancer Information Service (CIS) team of 

cancer information specialists are also available to 

answer questions via phone, live online chat, mail, 

and e-mail about cancer treatment and clinical trials, 

including CAM therapies. During FY 2005, CIS 

responded to more than 1,600 inquiries regarding 

CAM approaches for cancer.

Conducting Surveys and Focus Groups | 

OCCAM’s Communications and Outreach Program 

also assesses the opinions and interests of cancer 

researchers, CAM practitioners, and cancer patients 

regarding CAM research and assesses information 

needs via surveys and focus groups. Results from 

these explorations will be used to develop programs 

that are most helpful for these audiences. In FY 2005, 

OCCAM conducted a total of three focus groups 

with cancer researchers at the Annual Meeting of 

the American Society of Clinical Oncology and 

the 1st International Conference of the Society of 

Integrative Oncology.

NCI CAM Communications Programs

The PDQ Cancer Clinical Trials Registry contained a total of 64 (5 pediatric 

and 59 adult) active CAM clinical trials in FY 2005. (See the Appendix for the 

complete list of trials.) 

In FY 2005, the online PDQ cancer CAM 

treatment information summaries for health 

professionals were viewed 203,163 times. 

13

PART III

Training and conferences
NCI CAM Annual Report 2005

Leading Research Grant Writing

Workshop | Although rigorous scientific 

investigations in CAM can and should be conducted, 

the development of competitive research proposals 

in cancer CAM and securing federal funding is often 

challenging. To address challenges associated with the 

grant application process, OCCAM staff members 

lead occasional technical assistance workshops such 

as the June 2005 meeting Strategies for Success: How 

to Write a Grant in Cancer CAM. Scientists interested 

in CAM research were provided opportunities to 

learn about Federal and private grant application 

processes, participate in a mock grant review, and 

network with representatives from funding and 

matchmaking organizations. This was the second 

such workshop hosted by OCCAM. 

OCCAM has developed a companion document 

to the workshop that not only compiles information from existing NIH grant writing resources but 

also highlights some of the issues unique to CAM 

and CAM-related research areas. The document 

addresses many of the issues raised by NCI review 

committees and presents some of the potential solutions for applicants. The CAM grants manual was 

revised in June 2005 and is available for download 

on NCI’s Web site at http://www.cancer.gov/cam/

attachments/howtowrite.pdf.

In addition, OCCAM staff members are available to answer researchers’ questions and help identify 

appropriate mechanisms and funding opportunities.

Developing a Cancer CAM PracticeB ased R esearch N etwork | On 

September 26, 2005, OCCAM and the Bravewell 

Collaboration jointly hosted a meeting on the 

development of Practice-Based Research Networks 

(PBRNs) for the cancer CAM field. 

The U.S. Agency for Healthcare Research and 

Quality (AHRQ) defines a PBRN as an affiliated 

group of outpatient practices devoted principally to 

the primary care of patients that partner to investigate 

community-based practices. PBRNs may be local, 

regional, or national, and according to AHRQ , 140 

PBRNs are registered in the United States today.

The goal of this meeting was to bring together 

organizations that had developed such clinical 

research networks to discuss their experience in 

this area and the feasibility of establishing PBRNs 

composed of health professionals who include CAM 

methods in their practice settings. The primary audience for the meeting included representatives of 

the clinical network assembled by the Bravewell 

Collaboration, who were planning to develop such 

a network that would research topics relevant to the 

use of CAM in the management of cancer patients. 

NCI provides an array of training support programs on aspects of CAM research 

including grant writing workshops and scientific conference sponsorships. 

16
Participants at the planning meeting identified specific challenges to CAM research within the PBRN 

settings, such as:

Funding for placebos and drugs and their distribution may be a major feasibility issue for CAM 

clinical trials. In conventional medication studies, 

PBRNs rely upon pharmaceutical companies to 

provide the test agents. Companies that make 

CAM compounds (e.g., St. Johns wort, gingko 

biloba) lack the incentives of drug companies, 

so supplementary funding will be needed for a 

CAM clinical trials program.

CAM agents present serious quality control and 

batch-to-batch consistency issues, since natural 

products vary depending on where they are grown 

and which strain of plant is used. 

The three participating government funding 

organizations—NCI, AHRQ , and the National 

Center for Complementary and Alternative Medicine—also presented information about possible 

mechanisms to fund research projects which could be 

done by such a PBRN. As a result of this meeting, the 

Bravewell clinical network is forming a pilot group 

which will decide what types of data to collect, begin 

some basic data collection, and develop standardized 

protocols. The next phase would involve outreach to 

other community medical groups that have CAM 

practices. That expanded PBRN could conduct treatment outcomes studies and move toward clinical 

trials. Eventually, the CAM PBRN could become 

involved with other established PBRNs.

•

•

Supporting Scientific Conferences | 

A good example of NCI’s support of scientific cancer 

CAM conferences is the Society of Integrative 

Oncology’s (SIO) 1st International Conference in 

New York. OCCAM staff participate in program 

development and NCI provided conference grant 

support to SIO for its first ever conference. The 

meeting convened in November of 2004 and over 

600 people attended. The abstracts from the meeting 

are available in the December 2005 issue of the 

Journal of the Society of Integrative Oncology. 

Hosting OCCAM’s Invited Speaker

Series | With the goal of informing the NCI 

community about the variety of ongoing research 

in cancer and CAM, OCCAM created an Invited 

Speaker Series in which renowned experts present 

their groundbreaking research projects. During 

2005, Lorenzo Cohen, Ph.D., gave a presentation 

titled Traditional Chinese Medicine for Cancer: The 

Road to China. Cohen reported on the initial findings 

of the International Center of Traditional Chinese 

Medicine for Cancer, which is supported by an 

NCI planning grant and represents a collaboration 

between the University of Texas M. D. Anderson 

Cancer Center and the Fudan University Cancer 

Center in China.

Training and Conferences

17

PART IV

NCI Research in Complementary and 

Alternative Medicine
NCI CAM Annual Report 2005

(Includes Grants, CCOPs, Intram

Symptom / SideEffect Management

$12,902,337

Treatment

$20,595,440

Epidemiology

$5,908,404

Prevention

$81,670,738

1%

Alternative

Medical Systems

$627,676

.004%

Exercise

Therapies

$441,548

2%

Manipulative & Body

Based Methods

$1,571,808

8%

Mind-body

terventions

8,128,147

6%

Miscellaneous

$6,479,391

.0002%

Spiritual

Therapies

$24,552

1%

Alternative

Medical Systems

$627,676

.004%

Exercise

Therapies

$441,548

2%

Manipulative & Bodybased Methods

$1,571,808

6%

Miscellaneous

$6,479,391

Dietary Regimens

$11,790,913

17%

Food

$10,239,4

15%

Bioactiv

Food Chem

$10,179,

15%

Fat

$1,875,167

3%

Prevention

$81,670,738

67%

Treatment

$20,595,440

17%

Epidemiology

$5,908,404

5%

Symptom / Side-Effect 

Management

$12,902,337

11%

TOTAL (441 Projects)

$121,076,919

$140

$120

$100

$80

$60

$40

$20

$0

$119,900,000

$128,671,113

$121,076,919

 2003 2004 2005

fig 4. NCI’s CAM Expenditures FY03-FY05

FISCAL YEAR

MILLIONS

NCI CAM Research Projects

FY 2005 by Research Type

(Includes Grants, CCOPs, Intramurals, and Contracts)

fig 6.

Symptom / Side-Effect 

Management

$12,902,337

Treatment

$20,595,440

Epidemiology

$5,908,404

Prevention

$81,670,738

TOTAL (441 Projects)

$121,076,919

Minerals

$24,378,471

Vitamins

$10,866,734

Dietary 

$11,7

Food

$10,239,416 

fig 5.

Symptom / Side-Effect 

Management

$12,902,337

Treatment

$20,595,440

Epidemiology

$5,908,404

Preven

$81,67

TOTAL (441 Projects)

$121,076,919

Figure 3. NCI’s CAM 

Expenditures FY 2003-2005

Figure 4. NCI CAM Research Projects 

FY 2005 by Research Type*

* Includes Grants, Cooperative Agreements, Intramural Projects, and Contracts

20
NCI Research in Complementary and Alternative Medicine

Total Estimated Cancer CAM Research

Expenditure | Analysis of NCI’s FY 2005 CAM 

research portfolio shows that the agency has funded 

441 research projects of which either entirely focus 

or contain some portion that addresses CAM. These 

projects include an assortment of intramural projects 

and extramural grants, cooperative agreements, 

contracts, and supplements. The estimated total for 

NCI’s CAM research expenditures in FY 2005 is 

$121,076,919. (Figure 3) 

Breakdown by Research Type | The 

accompanying figure (Figure 4) shows the 

distribution of the NCI’s CAM research projects 

by: prevention, treatment, symptom/side effects 

management, and epidemiology. In FY 2005, 67 

percent of cancer CAM-related research projects 

were spent on various cancer prevention efforts, 

while treatment, symptom/side effects management, 

and epidemiology received 17 percent, 11 percent, 

and 5 percent, respectively.

Research

Portfolio Analysis

$0

 2003 2004 2005

FISCAL YEAR

NCI CAM Research Projects

FY 2005 by Research Type

(Includes Grants, CCOPs, Intramurals, and Contracts)

fig 6.

Symptom / Side-Effect 

Management

$12,902,337

Treatment

$20,595,440

Epidemiology

$5,908,404

Prevention

$81,670,738

TOTAL (441 Projects)

$121,076,919

69%

Nutritional

Therapeutics

$70,224,361

14%

Pharmacological

and Biologic

Treatments

$14,760,217

.0002%

Spiritual

Therapies

$24,552

1%

Alternative

Medical Systems

$627,676

.004%

Exercise

Therapies

$441,548

2%

Manipulative & Body

Based Methods

$1,571,808

8%

Mind-body

Interventions

$8,128,147

6%

Miscellaneous

$6,479,391

Minerals

$24,378,471

Vitamins

$10,866,734

Bioactive

Food Chemicals

$10,179,096

Dietary Regimens

$11,790,913

Food

$10,239,416 Fat

$1,875,167

TOTAL

$70,224,361

fig 5.

$12,902,337

Epidemiology

$5,908,404

69%

Nutritional

Therapeutics

$70,224,361

14%

Pharmacological and

Biologic Treatments

$14,760,217

.0002%

Spiritual

Therapies

$24,552

1%

Alternative

Medical Systems

$627,676

.004%

Exercise

Therapies

$441,548

2%

Manipulative & Bodybased Methods

$1,571,808

8%

Mind-Body

Interventions

$8,128,147

6%

Miscellaneous

$6,479,391

Figure 5. NCI CAM Therapies—FY 2005*

After each fiscal year comes to a close, OCCAM takes an in-depth look at 

NCI’s CAM research expenditures. Examination of NCI’s CAM portfolio is an 

important step in helping to identify research gaps in the field of cancer CAM 

and to encourage dialogue about the potential direction of future research. This 

yearly analysis is an exercise which reveals an estimated total amount of funding 

that goes to cancer CAM research projects (both intramural and extramural 

research) and provides breakdowns according to the type of research (prevention, treatment, side effects/symptom management, and epidemiology), CAM 

category, and cancer type. 21
NCI CAM Annual Report 2005

Breakdown by Major CAM Therapy 

Category | W ithin the FY 2005 NCI 

CAM portfolio, research projects examined 

a wide variety of CAM therapies. These CAM 

therapies were categorized into eight groupings: 

alternative medicine systems, energy therapies, 

exercise therapies, manipulative and body-based 

methods, mind-body interventions, nutritional 

therapeutics, pharmacological and biologic 

treatments, and spiritual therapies (Figure 5). The 

largest percentage of research projects investigated 

nutritional therapeutics. Nutritional therapeutics 

includes research on food (e.g., broccoli and 

berries), minerals (e.g., calcium and selenium), 

vitamins (e.g., vitamins C and D), bioactive food 

components (e.g., isoflavones and carotenoids), 

dietary regimens (e.g., caloric restriction and high 

fruits and vegetables), and fats (e.g., linoleic acid 

and omega-3). The accompanying pie-chart (Figure 

6) shows the distribution of projects by the subcategories. 

Breakdown by Cancer Type | NCI’s FY 

2005 research grants and cooperative agreements 

with CAM components can be categorized into 

twenty types of cancers. The largest amounts 

of cancer CAM research dollars spent were on 

prostate ($15,332,684), breast ($15,233,720), 

colorectal ($13,370,222), and lung ($7,774,659) 

cancers. Additionally, $15,141,134 was spent on 

the research of CAM for nonspecified cancers and 

thus could not be broken down further. For more 

information on the remaining categories, please see 

Figure 7, below.

Figure 7. NCI CAM Research Projects FY 2005 by Cancer Type*

*Excludes Cancer Center Support Grants (i.e. P30s), Special Programs of Research Excellence (SPORES, P50s), cooperative agreements that support the 

research bases for Community Clinical Oncology Programs (CCOPs, U10s) and their supplements.

Bladder ...................$781,447

Brain .......................$424,634

Breast .................$15,233,720

Cervical ...................$562,085

Colorectal ...........$13,370,222

Endometrial .............$300,626

Esophageal ..............$571,021

Gastric .....................$250,015

Head and Neck ....$1,362,157

Kidney .....................$552,321

Liver .....................$1,165,117

Leukemia ................$484,232

Lung .....................$7,774,659

Multiple Myeloma ...$203,850

Non-Specific ......$15,141,134

Ovarian ....................$145,152

Pancreatic ...............$635,393

Pediatric ..................$265,930

Prostate ..............$15,332,684

Skin, Melanoma ......$883,288

Skin, NonMelanoma ............$5,574,078

TOTAL ................$81,013,765

Figure 6. NCI’s FY 2005 CAM 

Nutritional Therapies Projects

TOTAL: $70,224,361

Epidemiology

$5,908,404

.0002%

Spiritual

Therapies

$24,552

6%

Miscellaneous

$6,479,391

Minerals

$24,378,471

34%

TOTAL

$70,224,361

Dietary Regimens

$11,790,913

17%

Food

$10,239,416

15%

Bioactive

Food Chemicals

$10,179,096

15%

Fat

$1,875,167

3%

Vitamins

$10,866,734

16%

Prevention

$81,670,738

67%

Treatment

$20,595,440

17%

Epidemiology

$5,908,404

5%

Symptom / Side-Effect 

Management

$12,902,337

11%

TOTAL (441 Projects)

$121,076,919

22
As is the case with other NCI research funding 

programs, NCI grants for CAM research often act as 

“seed money” that help institutions and organizations 

around the nation and the world build robust research 

programs in this growing field. Frequently, those 

same biomedical centers are then able to attract 

additional financial support for CAM scientific 

projects from other government agencies, non-profit 

institutions, and private industry. 

Wake Forest University School of Medicine 

(WFUSM) provides a good example of this phenomenon. “NCI has been quite instrumental, in 

several ways, in the success of Wake Forest’s CAM 

research programs in cancer,” noted Edward G. 

Shaw, M.D., professor and chairman of WFUSM’s 

Department of Radiation Oncology. 

The university hosts an NCI-designated Comprehensive Cancer Center led by Director Frank M. 

Torti, M.D., who has long had a great interest in the 

role of nutrition and CAM in cancer care. About 

5 years ago, the WFUSM Cancer Center obtained 

a funding supplement to its NCI support grant to 

explore areas of CAM and cancer. The initial focus 

was on basic research in areas such as the potential 

preventive role of vitamin D for which WFUSM has 

established a world-renowned reputation.

“The NCI supplement support grant* received 

about 5 years ago catalyzed rapid growth in the evidence-based CAM research at Wake Forest Health 

Sciences,” said Todd Thornburg, Ph.D., director of 

administration at the Cancer Center. “Specifically, 

one area initially supported—vitamin D effects on 

cancer—has grown to include both the clinical trials 

and basic science research for this line of inquiry.” 

This includes studying the combination of vitamin 

D and soy phytoestrogens for treatment of men with 

prostate cancer.

Wake Forest Cancer Center is also designated 

as a research base for one of NCI’s Community 

Clinical Oncology Programs (CCOP). “The general 

focus of CCOP research is in symptom management—things like fatigue, nausea, pain—and cancer 

prevention,” Shaw explained. “In the past few years, 

NCI has provided us with several ‘supplements’ to 

our CCOP grant specifically for doing scientificallybased, hypothesis-driven CAM clinical trials.”

Among the studies currently underway at 

WFUSM is a randomized study of a “nutraceutical” product called “Juice Plus”—capsules that are 

claimed to provide the same nutritional value as 

many servings of fruits and vegetables. The study 

will include 150 patients with head and neck cancer who have received conventional therapies who 

will receive either Juice Plus or placebo capsules 

to determine whether Juice Plus enhances patients’ 

immune systems which might reduce the incidence 

of second, primary tumors.

The Wake Forest CCOP is also testing other 

popular nutritional or herbal products, such as coenzyme Q10 and St. John’s wort, to relieve fatigue, hot 

flashes, and other side effects of cancer and conventional treatments.

The Wake Forest CAM research for cancer 

helped fuel WFUSM’s broader programs for “holistic and integrative medicine.” During 2005, more 

than 80 WFUSM faculty were pursuing academic 

work in this rapidly growing field, with over $25 

million in research funding and 115 peer-reviewed 

publications. “Overall funding for CAM research 

at Wake Forest has grown substantially in the last 

three years,” Thornburg noted. 

Among the various research projects underway 

are investigations funded by other NIH institutes, 

other agencies of the U.S. Department of Health 

and Human Services, nonprofit foundations, and 

industry. “Much of this funding was the result of 

the success of Wake Forest’s cancer CAM program 

and team-building that grew from the initial supplemental grant from the NCI,” Thornburg added. 

“Wake Forest has found that good complementary 

science can lead to good complementary medicine 

and that can be good news for cancer patients.”

*Supplemental support was provided from OCCAM and NCCAM though grant number 5U10CA081851.

NCI Research in Complementary and Alternative Medicine

NCI Grant Support:

The Gift That Keeps on Giving

23
M a j o r A c c o m p l i s h m e n t s i n 2 0 0 5

Fiscal Year 2005 saw the release of major findings which for the first time 

provided solid evidence that improvements in lifestyle and dietary interventions 

are feasible and can impact the recurrence of certain cancers. 
Significantly lowering dietary fat may lower 

the risk of recurrence of breast cancer in postmenopausal women treated for early-stage breast 

cancer. The findings are from the NCI-sponsored 

Women’s Intervention Nutrition Study (WINS), 

the first large-scale intervention trial to examine 

the influence of dietary fat on breast cancer outcomes in this population. 

“This could be the first randomized controlled 

clinical trial of a lifestyle intervention that impacts 

breast cancer outcomes,” said study lead author 

Rowan T. Chlebowski, M.D., Ph.D., of the Los 

Angeles Biomedical Research Institute at HarborUCLA Medical Center. He presented the preliminary findings for WINS at the May 2005 meeting of 

the American Society of Clinical Oncology.

The study included 2,437 women, aged 48 to 79, 

drawn from 37 U.S. medical centers. The study group 

was placed on a low-fat diet, averaging about 33 

grams of fat daily, while a control group consumed a 

standard diet that included approximately 52 grams of 

fat per day. Each group had previously received similar treatments for early-stage breast cancer, including mastectomy or lumpectomy with radiation, and 

postsurgical treatment protocols with chemotherapy 

and/or hormonal therapy, depending on whether 

patients had estrogen-dependent cancers. 

After 5 years, women on the low-fat diet 

showed a significant reduction in cancer recurrence 

compared with the control group: 9.8 percent vs. 

12.4 percent. Women on the low-fat diet who had 

been previously treated for a type of breast cancer 

that is not estrogen-responsive (ER)—a form of 

the disease that is typically associated with a greater 

likelihood of recurrence—had a 42-percent reduced 

risk of recurrence compared with those on a standard diet. 

“The effect on ER-negative disease is a surprising and potentially important observation regarding 

breast cancer,” said Dr. Peter Greenwald, director of 

NCI’s Division of Cancer Prevention. “These data 

demonstrate the possible importance of considering 

dietary factors in cancer therapy trials.” 

Final results from WINS are expected to be 

published in 2006 or early 2007. “We also hope our 

results will encourage cancer researchers to look at 

different pathways suggested by the effectiveness of 

dietary interventions,” said Chlebowski. “By exploring those avenues, they may identify targets for 

interventions by other small molecules.”

Chlebowski is also hopeful that, if WINS and 

similar studies prove the benefits of various dietary 

prevention interventions for cancer, it will lead 

health insurers, including Medicare, to provide 

coverage for such approaches. “That would be a 

big thing,” he believes. “The WINS dietary intervention would cost a patient about $1,000 a year 

which they’d have to pay themselves currently.” 

He noted that Medicare currently reimburses for 

dietary interventions for patients with renal disease 

and diabetes but not for heart disease or cancer. 

Major Accomplishments in 2005

Low-Fat Diet May Lower Risk 

of Breast Cancer Recurrence

Division of Cancer Prevention

Findings from the WINS study were recognized 

by the American Society of Clinical Oncology as 

a highlight at their 2005 Annual Meeting.

NCI Research in Complementary and Alternative Medicine

25
NCI CAM Annual Report 2005

In spring 2007, researchers expect to announce 

the long-awaited results from the Women’s Healthy 

Eating and Living (WHEL) study, a multicenter, 

randomized clinical trial testing the hypothesis that 

a high vegetable and high fiber diet might lower the 

risk for recurrence and death from breast cancer.

The WHEL study, which is supported by an 

R01 grant from NCI, enrolled 3,088 women with 

early-stage invasive breast cancer between 1995 and 

2000. The women were assigned to either a control 

group or an intensive diet intervention group who 

were counseled to maintain a daily diet of 5 vegetable 

servings, 16 ounces of vegetable juice, 3 fruit servings, 

30 grams of fiber, and 15–20 percent dietary fat. The 

goal was to substantially increase levels of circulating 

carotenoids in the blood, because previous research 

showed that low-levels of carotenoids are associated 

with higher rates of breast cancer recurrence.

Although the final results will not be known 

until next year, WHEL has already reported spectacular success in getting women to adopt the rigorous diet, said Principal Investigator John P. Pierce, 

Ph.D., director of the Cancer Prevention and Control Program at the University of California, San 

Diego (UCSD) Cancer Center. “We’ve achieved 

major changes in behavior,” he notes. 

After 6 years of follow up, participants in the 

intervention group were eating each day, on average, about 4.5 vegetables, drinking 6 ounces of vegetable juice, and ingesting 26 grams of fiber. Even 

more significant, “we have doubled the circulating 

carotenoid levels in the blood which is much more 

than any other study has accomplished previously 

and will allow us to properly test the hypothesis,” 

Pierce added.

The WHEL study achieved these remarkable 

lifestyle changes relying primarily upon telephone 

counseling from trained lay persons. “In designing 

the protocol, we asked people who they would like 

to talk with 18 times over the course of a year during 

the intensive intervention phase,” Pierce recalled. 

Possible choices included a nutritionist, their doctor, 

physical therapist “or your personal chef,” he said. 

“They always picked the latter.” As a consequence 

of using phone counseling rather than clinic visits, 

“there is a considerable cost savings to our intervention,” he noted. 

The WHEL study took blood and other tissue 

samples from participants on five different occasions “so we have an outstanding biological samples 

database to study recurrence,” Pierce explained. 

A supplement to the study funded a survey of 

WHEL participants that focused on their past and 

current use of various CAM modalities, including 

mind-body practices, energy-based therapies, and 

alternative medical systems, such as homeopathy 

and naturopathy. 

The WHEL investigators are presently summarizing the responses from the interviews and 

will report on the frequency of use of different 

CAM modalities, reasons for using these modalities, and their patterns of disclosing CAM use to 

healthcare providers. The study has also developed 

one of the largest databases on nutritional supplements and will report on trends and influences on 

usage over time.

Major Accomplishments in 2005 

WHEL Study Testing High Vegetable 

Diet for Breast Cancer Recurrence

Division of Cancer Prevention

26
NCI Research in Complementary and Alternative Medicine

C a r o t e n o i d s , like those found in green tea, are being studied 

for their potential in reducing breast cancer recurrence.

27
NCI CAM Annual Report 2005

Patients with early, low-grade prostate cancer benefited from intensive lifestyle changes that 

included a “vegan” diet with lots of fruits and vegetables, moderate exercise, and stress-reducing yoga. 

After one year of this regimen, average levels of 

prostate-specific antigen (PSA)—a marker of disease progression—decreased by 4 percent in these 

patients while average PSA levels increased 6 percent among a control group of similar patients who 

didn’t follow the new lifestyle regimen, according 

to a small study published September 2005 in the 

Journal of Urology.

Patient recruitment for this study was limited 

to men who had chosen not to undergo any conventional treatment, which provided an unusual 

opportunity to have a nonintervention, randomized 

control group to avoid the confounding effects of 

interventions such as radiation, surgery or androgen 

deprivation therapy. A total of 93 volunteers with 

serum PSA levels of 4 to 10 ng/ml, and cancer 

Gleason scores less than 7, were randomly assigned 

to either an experimental group that was asked to 

make comprehensive lifestyle changes or to a usual 

care control group.

“The issue of diet and nutrition and supplements are of high priority to patients and their families,” noted Peter R. Carroll, M.D., chair of Urology 

at University of California, San Francisco (UCSF). 

“We’ve done additional work which has shown at 

least 40 percent of men diagnosed with prostate cancer are engaged in some type of alternative therapy 

usually in conjunction with conventional therapy 

but sometimes independently.” Carroll was co-leader 

of the study along with UCSF Professor and noted 

author Dean Ornish, M.D. The study was funded by 

grants from NCI and other organizations.

Carroll, Ornish, and their colleagues are following up with an even closer look at the genetic changes 

produced by such lifestyle changes on patients’ prostate glands. He said, “The trial design we’ve chosen 

focuses on men similar to those in the first study. In 

the new study we biopsy the prostate initially, do 

a gene expression array on benign and malignant 

tissues obtained, treat them with alternative agents, 

re-biopsy the prostate after 3 to 4 months, and then 

perform another gene expression array. We want to 

better test the hypothesis that such therapy has a 

real effect on the prostate microenvironment.”

Studying the impact of diet, exercise, and stress 

reduction on prostate micro-environment will provide more definitive data on such interventions. The 

researchers are using this same approach in a separate study of lycopene, found in tomato products, 

and omega-3 fatty acids and their effect on prostate 

cancer. It can also be used to study other potential 

preventive agents, Carroll commented.

Major Accomplishments in 2005 

Intensive Lifestyle Changes Show 

Benefits for Prostate Cancer

Division of Cancer Control and Population Sciences

28
A d d r e s s i n g N C I ’s S t r at e g i c A r e a s

The remaining research highlights are selected from the over 400 CAM research projects NCI 

supports at laboratories throughout and United States and the world. These research projects 

are organized under the major goals of The NCI Strategic Plan for Leading the Nation.

NCI’s Strategic Plan can be found on the Web at http://strategicplan.nci.nih.gov.
NCI CAM Annual Report 2005

Understanding the Causes 

and Mechanisms of Cancer

Cancer is a complex set of diseases that scientists are 

striving to understand from multiple perspectives. Research 

that improves our understanding of its causes and the 

mechanisms that underlie its development—from assessing 

cancer risk to explaining the process of metastasis—is 

essential to our ability to develop and apply interventions to 

preempt cancer initiation and progression.

30
NCI Research in Complementary and Alternative Medicine

The milk thistle plant has been used to treat 

ailments for more than two thousand years. Over 

the next few years, Rajesh Agarwal, Ph.D., and his 

colleagues at the University of Colorado Health 

Sciences Center hope to learn whether a compound 

from the plant’s seeds might help prevent prostate 

cancer. 

The compound, silibinin, is being evaluated 

in a Phase II clinical trial. Participants will take 

the compound for 4–8 weeks prior to undergoing 

surgery to remove the prostate. The researchers will 

then determine whether the compound reaches the 

prostate and assess certain biological markers associated with the proliferation of cells and cell death. 

“The clinical trial is very exciting for us,” said 

Agarwal, who has been investigating silibinin and 

silymarin—the crude form of silibinin—with some 

other compounds in cells and animals for nearly 

two decades. “We have succeeded in taking silibinin 

from the bench to the bedside in prostate cancer.” 

A Phase I clinical trial is also being planned to 

test the compound’s potential for preventing skin 

cancer. Based on his research, Agarwal believes silibinin may be useful against other common cancers as 

well, including colon and lung. 

Silymarin and its main biological ingredient, 

silibinin, have been used in Europe for decades to 

treat liver diseases. In terms of safety, silymarin and 

silibinin are generally well tolerated and have no toxic 

effects. Silymarin is sold as a dietary supplement on 

the Internet and in the United States and Europe. 

In a project funded by NCI, Agarwal and his 

colleagues are now investigating the anti-tumor promoting effects of silibinin at the cellular, biochemical, and molecular levels. “Our goal is to understand 

the mechanisms that help protect against the development of tumors,” said Agarwal. 

Agarwal also plans to conduct future studies 

on whether silibinin may also increase the efficacy 

of chemotherapy drugs and counteract some of the 

toxicity of these drugs.

Understanding the Causes and Mechanisms of Cancer 

Milk Thistle and Prostate Cancer: 

Moving from Bench to Bedside 

Division of Cancer Prevention

M i l k T h i s t l e ,

silybum marianum

31
NCI CAM Annual Report 2005

In recent years, his laboratory has identified 

a number of functions for methyl selenium in 

terms of regulating the blood vessel endothelial 

cell responses to angiogenic stimulation and controlling the production of angiogenic stimulators 

by the cancer cells. In addition, his laboratory and 

that of Clement Ip, Ph.D., of Roswell Park Cancer 

Institute have found that certain concentrations of 

methyl selenium decreases androgen and its receptor-signaling activities that are critical for prostate 

cancer. His group also discovered that this form of 

selenium may enhance the treatment efficacy of 

chemotherapeutic drugs. 

In the NCI-funded study, Lu and his colleagues expect to validate the role of several target 

proteins believed to be involved in mediating the 

inhibition of blood vessels by methyl selenium. The 

results, the researchers believe, will lay the foundation for future work to investigate how methyl 

selenium reacts and interacts with these target 

proteins to bring about biochemical and cellular 

changes related to cancer prevention. 

During the 1990s, the results of a landmark cancer prevention trial in the United States 

strengthened the hypothesis that the trace mineral 

selenium, as a nutritional supplement, is a safe and 

effective preventative agent against the development 

of certain solid cancers, including prostate, lung, and 

colon. More recently, a growing body of evidence 

from epidemiological, ecological, and clinical studies suggests that selenium may modify the risk of 

these cancers. 

Junxuan Lu, Ph.D., of the University of Minnesota and his colleagues have undertaken an investigation, sponsored by the NCI, of the mechanisms underlying the hypothesized effect that selenium might 

have on angiogenesis, the process by which blood 

vessels are created to supply tumors with oxygen and 

essential nutrients. The researchers are testing several 

types of mono-methylated selenium compounds that 

can increase the production of methylselenol, which 

is considered the active form of selenium for cancer 

chemoprevention in the body. 

“We think that this type of selenium has very 

favorable attributes for cancer prevention,” said Lu, 

noting that different forms of selenium probably 

have different functional properties. “A lot of work 

by our group and collaborators in last decade has 

focused on identifying these different functions, and 

we certainly think some forms are better for cancer 

prevention than others.” 

Understanding the Causes and Mechanisms of Cancer 

Selenium and Cancer Prevention: 

Investigating Mechanisms 

of Anti-angiogenesis 

Division of Cancer Prevention

32
NCI Research in Complementary and Alternative Medicine

Accelerating Progress 

in Cancer Prevention

Prevention is our first line of defense against cancer. Efforts 

to prevent cancer focus on understanding and modifying 

behaviors that increase risk, mitigating the influence of genetic 

and environmental risk factors, and interrupting cancercausing processes through early medical intervention. 

33
a l p h a - l i n o l e n i c a c i d ( a l a ) , 

an essential omega-3 fatty acid

S p a n i s h S a r d i n e , Sardinella Aurita

34
NCI Research in Complementary and Alternative Medicine

Prostate cancer is far more prevalent in Northern Europe and the United States than in Asia, 

Alaska and Africa. Studies suggest that one reason 

for low incidence of prostate cancer in those regions 

could be the abundance of omega-3 polyunsaturated 

fatty acids (PUFAs) present in the fish-based diets 

consumed by their populations.

Jose Halperin, M.D., from the Harvard Medical School and the Dana Farber/Harvard Cancer 

Center, has identified how PUFAs might interfere 

with carcinogenesis in the prostate. Currently, the 

most promising candidate among the “good” fatty 

acids is eicosapentaenoic acid (EPA), the primary 

PUFA found in sea fish. Laboratory and animal 

studies have shown that EPA interferes with the 

translation process of some oncogenes and thus 

slows prostate cancer growth. EPA also seems to 

trigger the expression of some protective proteins 

that actually kill tumor cells.

There is every reason to hope that the protective 

effect of EPA also works in humans, Halperin said. 

Scientists at Harvard conducted a 12-year prospective population study in about 50,000 men, whose 

risk of metastatic prostate cancer was cut in half 

when they consumed fish three times a week. 

Halperin is now conducting an ambitious NCIfunded study to confirm the impact of EPA on prostate cancer. He will enroll men scheduled to have 

prostatectomies (removal of the prostate gland) in 

a prospective trial, and give them daily doses of fish 

oil (70 percent EPA) or placebo for several weeks 

before surgery. Their tumors will ultimately be analyzed for cellular evidence that the EPA has been 

inhibiting translation of oncogenes in the tumors, 

just as it does in cancer cells in the laboratory. 

The patients’ blood will then be analyzed for the 

content of n-3 and n-6 fatty acids, and this information will be compared with biological markers that 

identify how translation has been affected, as well 

as with the clinical Gleason score used to evaluate 

prostate disease from biopsy tissue. Finally, he will 

analyze a collection of tumor tissue taken over a 

10-year period, to better track translation and the 

progression of prostate cancer.

“This is a tremendously exciting area of cancer 

research which could have an enormous impact 

on public health,” said Halperin. “I hope our work 

can help increase the momentum for large clinical 

trials. Prostate cancer is a major disease in the West, 

and while we haven’t shown that fish oils prevent 

it altogether, they do appear to influence how it 

progresses. We may be looking at a natural answer 

for prevention and control of prostate cancer.”

Accelerating Progress in Cancer Prevention 

Fish Diet May Have Role in 

Preventing Prostate Cancer

Division of Cancer Prevention

35
NCI CAM Annual Report 2005

Endometrial cancer is the most common reproductive cancer in the United States, but occurs far 

less frequently in China. Chinese women also have 

lower levels of the hormone estrogen—and they 

consume much more soybean-based food—than do 

their American counterparts. 

Scientists are trying to fit the pieces of this puzzle together. Beginning in 1997, Principal Investigator Xiao Ou Shu, M.D., Ph.D., and her colleagues 

at Vanderbilt University’s Ingram Cancer Center 

began a pilot epidemiological study of endometrial 

cancer in China, working in collaboration with 

researchers at the Shanghai Cancer Institute. They 

initially recruited about 500 women with endometrial cancer and also a set of case-matched healthy 

individuals, to explore lifestyle and diet factors, 

including soy foods, that researchers believed might 

be involved in development of endometrial cancer.

NCI support allowed Shu and her colleagues to 

recruit more women and to explore genetic susceptibility to this malignancy. By the time they closed 

enrollment in 2005, 1,204 cases and 1,212 controls 

had joined what was now called the Shanghai Endometrial Cancer Study (SECS). Some of the study’s 

findings have already been published and Shu expects 

the DNA data from study participants will provide 

some important insights into how the progression 

of the disease might be affected by the interaction 

between an individual’s genetic susceptibility to the 

disease and lifestyle factors such as soy and fiber in 

the diet, physical activity, obesity, and the history of 

weight change before the disease developed.

Some of the published findings include evidence that soy food intake—in a number of different forms—cuts risk of endometrial cancer by 33 

percent. They also found that higher intake of vegetables, especially green and yellow, was associated 

with more than a 30 percent risk reduction. 

This study showed that both overall obesity and 

central-body obesity are related to an elevated risk of 

endometrial cancer, with the latter condition being 

associated with a higher risk. More importantly, the 

study showed that weight gain during adulthood, 

even among current non-obese women, increases 

the risk of the disease. The investigators also found 

that life-time physical activity confers some protection against endometrial cancer. Women who exercised in adolescence and adulthood were 37 per cent 

less likely to develop endometrial cancer.

Accelerating Progress in Cancer Prevention 

Preventive Role of Soy Food in Endometrial 

Cancer Explored in Chinese Study 

Division of Cancer Control and Population Sciences

36
NCI Research in Complementary and Alternative Medicine

For many years, in the popular press as well as 

in medical journals, a controversy has arisen over the 

healing powers of “antioxidants,” which are plentiful in certain fruits and vegetables. One abundant 

natural source of antioxidants is berries, including 

black raspberries.

The laboratory of Gary Stoner, Ph.D. at Ohio 

State University is seeking to discover whether black 

raspberries may help to prevent esophageal cancer. 

Effective chemoprevention for this disease would 

be significant, since by the time esophageal cancer is 

diagnosed in most patients, it has already metastasized, and their survival rate is less than 10 percent.

In previous work, Stoner showed that some 

cruciferous vegetables contain an ingredient known 

as phenethyl isothiocyanate, which blocks tumors 

from getting started in the esophagus. Stoner 

believes berries may have a natural substance that 

not only blocks these cancers from starting, but also 

inhibits the growth of cells that have already begun 

the carcinogenic process, thus preventing the disease 

from progressing to more advanced stages. 

His NCI-funded study uses a rat model in 

which esophageal cancer is induced by the carcinogenic substance N-Nitrosomethylbenzylamine 

(NMBA). This is a relevant carcinogen, 

because it is found in the diets of Chinese citizens who are at high 

risk for esophageal squamous 

cell carcinoma. In this animal 

study, dietary freeze-dried 

black raspberries were shown 

to block and suppress cancer 

development in rats. The blocking agents in berries interfere with NMBA’s ability 

to initiate tumors, Stoner explained. The suppressing 

agents also work on precancerous cells by inhibiting 

their growth and stimulating their death. Finally, the 

berries prevent the formation of new blood vessels 

that feed developing tumors, he added. 

Work in the lab of one of Stoner’s colleagues has 

developed a reliable method for producing extracts 

from black raspberries. Studies with these extracts 

suggest that the anthocyanins in the berries—the 

compounds that give them their color—are at least 

partially responsible for their anticancer activity, 

Stoner noted.

The results in the rat esophagus study have 

led to a human clinical trial in China to evaluate 

the ability of dietary black raspberries to prevent 

esophageal squamous cell carcinoma.

 “Berries appear to contain an effective ‘cocktail’ of chemopreventive agents,” said Stoner. “They 

could have a significant role in the prevention of 

esophageal cancer. We hope not only to demonstrate that they work but to show persuasively why. 

We may also be able to demonstrate a synergistic 

effect, by testing the black raspberries along 

with dietary isothiocyanates.”

Accelerating Progress in Cancer Prevention 

Prevention of Esophageal 

Cancer with Berries

Division of Cancer Prevention

B l a c k R a s p b e r r i e s

contain compounds that offer 

potential in cancer prevention.

37
NCI CAM Annual Report 2005

In 1996, Stephen Lam, M.D., a senior scientist at the British Columbia Cancer Research 

Centre (BCCRC), attended a medical conference 

in Beijing, China, where he heard the presentation of results from a clinical trial of Anti-Cancer 

and Preventative Herbal Agent (ACAPHA) as 

a chemoprevention agent for esophageal cancer. 

ACAPHA is a combination of six herbs1 used in 

traditional Chinese medicine. The Chinese research 

team found that the use of ACAPHA in patients 

with esophageal dysplasia reduced the incidence of 

invasive cancer by 40 to 50 percent.

Lam, who is the principal investigator of 

the Lung Health Study chemoprevention group 

at BCCRC, was impressed by these results. His 

research team joined the Chinese team on a follow-up study, which found that the patients who 

had taken ACAPHA also had a reduced incidence 

of lung cancer. Lam decided to test ACAPHA as 

a chemoprevention agent for lung cancer in a randomized controlled trial in North America.

The NCI-funded trial began in January 2003 and 

will finish by the end of 2007. During the 5-year trial, 

more than 2,000 former smokers will be screened 

for bronchial intraepithelial neoplasia (IEN)—a precancerous condition of the lung—using a multistep 

process. First, the investigators will examine sputum 

samples for abnormal cells. If abnormal cells are 

found, the patient will undergo fluorescence bronchoscopy. If the investigators observe any abnormal 

cells in the airways during bronchoscopy, the region 

will be biopsied for pathologic analysis.

“In order to find people with precancerous 

lesions, we have to screen a lot of former heavy 

smokers who are at high risk for lung cancer, 

because not every smoker will develop lung cancer,” 

explained Lam.

Ninety patients with identified IEN will be 

randomly assigned to receive either ACAPHA or a 

placebo for six months. All patients will be evaluated with both repeated bronchoscopy and CT 

scans, and the regression and progression rates of 

precancerous lesions will be compared between the 

study groups. Because the investigators are blinded 

to the results until the end of the trial, preliminary 

data are not yet available. However, results from 

a preliminary Phase I/II open trial performed by 

the group at BCCRC indicated that ACAPHA is 

potentially effective in reversing pre-existing dysplastic lesions in the bronchus.

Accelerating Progress in Cancer Prevention 

Chinese Herbal Agents Tested 

in Lung Cancer Prevention

Division of Cancer Prevention

1. Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus, and 

Dioscorea bulbifera

38
P r u n e l l a V u l g a r i s ,

one of the six herbs in ACAPHA.

39
NCI CAM Annual Report 2005

Sequels to blockbuster movies usually don’t do 

as well as the original—who remembers “Jaws III”? 

But the Physicians Health Study II (PHS II) on 

the possible prevention role for vitamins in cancer 

and cardiovascular disease (CVD) may affect the 

practice of medicine just as powerfully as did the 

Physicians Health Study I (PHS I). 

In 1988, PHS I researchers announced the finding that daily, low-dose aspirin decreased the risk of 

a first myocardial infarction by 44 percent which 

helped focus the role of aspirin in primary prevention. In 2007 or 2008—about 20 years later—PHS 

II is expected to provide definitive evidence about 

whether or not long-term use of supplements for 

Vitamin E, C, or multivitamins are effective in the 

primary prevention of cardiovascular disease, cancer, 

and age-related eye disease.

“We believe our studies will be useful regardless 

of the outcome of the study since these vitamins are 

widely used by the general public and we need to 

better understand if they can prevent chronic diseases,” noted Co-Principal Investigator J. Michael 

Gaziano, M.D., Brigham and Women’s Hospital 

in Boston. Unlike drugs, dietary supplements don’t 

go through rigorous clinical testing and approval by 

the U.S. Food and Drug Administration, he added. 

“It’s a multibillion dollar industry and the public 

deserves to know one way or the other what is the 

utility of taking these supplemental agents.”

PHS II began in 1997 with industry support. It 

eventually enrolled almost 15,000 patients 50 years 

or older who were randomly assigned to receive 

either placebos or one of 16 possible combinations 

of vitamin C (500 mg) daily, vitamin E (400 IU) on 

alternate days, and a multivitamin (Centrum Silver) 

daily. NCI provided funding for the second 5 years 

of the study which will conclude in early 2007. 

Primary endpoints for PHS II are assessing the 

impacts of vitamin C, vitamin E, and a multivitamin 

on the primary prevention of: cardiovascular disease; 

prostate and colon cancer; aging-related eye disease; 

and early cognitive decline.

“These agents have the potential to be part of 

our prevention armamentarium” for chronic disease 

along with smoking cessation, diet, and exercise, 

Gaziano commented. “Based on what we know from 

observational data, if there are any effects of these 

dietary interventions, the effects will be modest. It 

would be important not to give anyone the impression that they could take a supplement of some kind 

instead of exercising or stopping smoking.”

Accelerating Progress in Cancer Prevention 

Physicians Health Study II: 

Prevention Trial of Vitamins

Division of Cancer Prevention

T h e P h y s i c i a n s H e a l t h S t u d y I I

is assessing the impacts of vitamin C, vitamin E, 

and a multivitamin on the primary prevention of 

cardiovascular disease, prostate and colon cancer, 

aging-related eye disease, and early cognitive decline.

40
Developing Effective and 

Efficient Treatments

The development of more efficient and effective cancer 

treatments—that target cancer cells while leaving 

surrounding healthy tissue unharmed—is at the heart 

of NCI’s research agenda. We strive to develop welltolerated, individualized therapies that are tailored to 

specific features of a patient’s cancer. 

41
NCI CAM Annual Report 2005

During treatment with chemotherapy, cancer 

cells can develop resistance to the drugs in use, and 

most of the factors behind the development of drug 

resistance remain to be explained. 

One aspect of resistance that is not well understood is what role the nutritional environment of the 

cell plays. Gary Johanning, Ph.D., and his research 

team from M.D. Anderson Cancer Center have 

undertaken laboratory studies to examine the role 

of folate depletion in the development of lung and 

ovarian cancer cells resistance to cisplatin, a commonly-used chemotherapy agent.

“If our current and follow-up studies are successful, a rationale for clinical trials aimed at evaluating the influence of high-dose folic acid supplementation on resistance to chemotherapy in cancer 

patients would be established,” said Johanning.

The researchers first propagated lung and ovarian cancer cells in normal culture media and in media 

acutely depleted of folate, and they then exposed the 

cells both to cisplatin. The number of cells surviving 

the exposure to cisplatin was significantly greater in 

the depleted media, though the magnitude of resistance varied between cell lines. 

The researchers then performed cDNA microarray analysis to screen for genes that were differentially expressed in cells grown in normal and 

depleted media. Several genes were identified whose 

expression is altered by folate levels in the presence 

of cisplatin. A paper reporting these results has 

been a published in 2006 in the journal Nutrition 

and Cancer. 

Follow-up studies will examine the relationship 

between folate depletion and cisplatin resistance 

in greater detail, including possible alterations in 

molecular transport, DNA damage during the development of resistance, and changes in gene expression 

after supplementation with folate. All experiments 

will use very high doses of folate, which correspond 

to megadose supplementation in humans. 

The investigators hope to eventually test 

whether depletion and supplementation of folate 

have the same effects in animal models. “If folic acid 

depletion is ultimately found to increase resistance 

to cisplatin, and megadose supplementation is found 

to block resistance to these agents. Then, a simple 

and inexpensive approach to prevent, at least in part, 

the resistance that limits the effectiveness of chemotherapy will be realized,” Johanning added.

Developing Effective and Efficient Treatments 

Folate Depletion and Cancer 

Cell Resistance to Cisplatin

Division of Cancer Treatment and Diagnosis

f o l i c a c i d is being 

studied as a potential aide in 

decreasing cancer cell resistance 

to chemotherapy.

HO

N

N

N

N

NH2

NH

NH

O

O

HO

O

OH

42
NCI Research in Complementary and Alternative Medicine

Researchers from the University at Buffalo 

(New York) Schools of Nursing, Medicine and Biomedical Sciences, and Public Health and HealthRelated Professions are conducting a pilot clinical 

study that addresses the controversy over whether or 

not dietary multivitamin/mineral supplements that 

include antioxidants should be taken during radiation therapy for cancer. The study is funded by NCI’s 

Division of Cancer Treatment and Diagnosis.

“One side of the debate argues that antioxidant 

vitamins and minerals repair cells, while the purpose 

of cancer therapy is to destroy cancer cells. Consequently, antioxidants may interfere with treatment 

by trying to repair cancer cells,” explained Principal 

Investigator Jean K. Brown, Ph.D., RN, FAAN, 

Associate Dean for Academic Affairs and Nursing 

Professor at Buffalo. Others believe that antioxidants 

help repair healthy cells damaged by radiation and 

that the effects of collateral damage from cancer therapy may be minimized. “The bottom-line is nobody 

knows the answer to the controversy,” she added.

Brown and her colleagues designed the doubleblind, randomized study to try to replicate “what we 

believe patients might already be doing in their selfcare management relative to taking multivitamin/

mineral supplements that include antioxidants.” 

Starting in January 2006, they began enrolling prostate cancer patients who are receiving radiation into 

one of three groups of the study: one group receives 

placebos; the second receives a regular “one-a-day” 

Developing Effective and Efficient Treatments 

Scientists Study Response to Multivitamins/

Minerals During Cancer Therapy

Division of Cancer Treatment and Diagnosis

dose multivitamin/mineral supplement; and the 

third group receives a “one-a-day” dose vitamin/

mineral supplement with antioxidant components 

increased to about one-half of upper tolerable limits 

set by the National Academy of Sciences.

“We’re looking primarily at the effects of antioxidants but secondarily at the impact of vitamins 

and minerals on the treatment,” Brown noted. The 

researchers will track tumor response by monitoring 

the patients prostate-specific antigen (PSA) levels 

for 18 months and beyond. “We decided to also look 

at effects at a cellular level, so we’re doing a series 

of assays on oxidative damage among the three 

groups,” she added. “We’re also looking at immune 

function, how side effects vary, nutritional status, 

and quality of life.”

The researchers plan to enroll up to 60 patients in 

the Phase II study, and Brown hopes to have results 

in two years. They will then pursue a larger, multisite study to confirm and expand upon the findings. 

Brown commented: “I believe the study will answer a 

question that physicians are dealing with from their 

cancer patients every day: ‘Should I or should I not 

continue to take multivitamins during my treatment?’ 

We really need the scientific data to advise patients 

about what they should be doing.”

43
M i n d f u l n e s s - B a s e d S t r e s s R e d u c t i o n 

( M B S R ) has been shown to reduce symptoms of stress and 

mood disturbance in some cancer survivors.

44
NCI Research in Complementary and Alternative Medicine

The focus of a pilot study at Loyola University 

of Chicago is the evaluation of the potential for 

the practice of “mindfulness” to improve both the 

psychological and immune outcomes for breast 

cancer patients.

Funded by NCI’s Division of Cancer Biology 

(DCB), the study has investigated the effects of 

a Mindfulness-Based Stress Reduction (MBSR) 

program, developed by Jon Kabat-Zinn, Ph.D., 

in women recently diagnosed with breast cancer. 

“MBSR had been shown, by a number of other 

investigative groups, to reduce symptoms of stress 

and mood disturbance in heterogeneous samples 

of cancer survivors,” reported Principal Investigator Linda W. Janusek, Ph.D., RN, and professor 

at Loyola’s School of Nursing. “In HIV-infected 

individuals, we have shown MBSR to improve 

immune function. Thus, there was a strong rationale 

to evaluate MBSR as a means by which to improve 

cancer-related immune dysregulation and psychological distress.”

The study began in Fall 2003 and enrolled 40 

women who completed the MBSR program at the 

same time that they underwent their usual cancer care, while a comparison group of 35 women 

received only their usual cancer care. Karen Chroniak, Ph.D., a clinical psychologist, led the 8-week 

MBSR program and instructed the women in the 

practice of mindfulness. Janusek explained: “Mindfulness meditation is a non-judgmental awareness 

of the present moment and is learned through practices such as sitting and walking meditation, body 

and breath awareness, and mindful yoga. With 

practice, mindfulness is brought to one’s daily life 

and allows an individual to respond mindfully to life 

events, instead of reacting in an automatic fashion. 

In essence, mindfulness becomes a way of living.” 

There are sound biological links between the 

brain and the immune system that provide a scientific rationale for evaluating whether behavioral interventions, such as mindfulness, can boost 

immune function. “Our emotions produce chemical changes in our brains, which in turn, activate 

neurochemical processes that have the potential 

to alter immune function,” according to Janusek. 

“Clear biological connections link the brain and 

immune cell populations.” By reducing the emotional response to negative life events, including cancer diagnosis and treatment, mindfulness 

practice may prevent stress-related suppression of 

immune function. 

The study completed enrollment in June 2006, 

and Janusek and her colleagues are starting to 

analyze the data. In the previous study on HIV 

patients, they demonstrated an increase in natural 

killer cell numbers circulating in those practicing 

MBSR. If the new study finds similar benefits for 

breast cancer patients, Janusek plans to conduct a 

larger, randomized clinical trial to further study 

breast cancer patients.“We will expand both our 

immune and psychological outcomes and will also 

evaluate neuroendocrine measures, biorhythms, 

and sleep,” she said.

Developing Effective and Efficient Treatments 

Meditation May Enhance Immune 

System for Breast Cancer Patients

Division of Cancer Biology

45
NCI CAM Annual Report 2005

Immunotherapy as a treatment is meant to 

stimulate or restore the ability of the immune system to fight cancer, infections, and other diseases. 

Experimental immunotherapies under development for the treatment of cancer include monoclonal antibodies, vaccines, and substances such as 

interleukins, which can improve the body’s natural 

response to disease.

Inflammation—the redness, heat, and swelling 

in injured tissue caused by white blood cells fighting 

an infection—occurs as part of the normal immune 

response. Some researchers working in the field of 

cancer immunotherapy have postulated that inflammation can augment anti-tumor immune responses.

Julie Ostberg, Ph.D., and Elizabeth Repasky, 

Ph.D., from Roswell Park Cancer Institute (RPCI), 

are investigating the thermal aspect of the inflammation. They have proposed that fever-range (39–

40°C) thermal stimulation of the inflammatory 

activity of granulocytes such as polymorphonuclear 

neutrophils (PMNs) helps to eliminate cancer cells 

in the body and is at least part of the basis by which 

mild, fever-range hyperthermia helps to control 

tumor growth. Their current research, funded by 

NCI’s Division of Cancer Biology, is using in vivo 

tumor models in mice to obtain cellular and molecular data that will test this hypothesis and help to 

identify potential mechanisms by which the thermal 

microenvironment enhances PMN activity.

Developing Effective and Efficient Treatments 

Whole-Body Hyperthermia (Fever) 

May Help Tumor Control

Division of Cancer Biology

“Our group had done a Phase I trial to show 

that whole-body hyperthermia was safe to use in 

terminally ill cancer patients,” said Ostberg. “Now 

we’re going back to the bench and trying to really 

figure out what the cellular and molecular mechanisms are behind the anti-tumor potential of this 

treatment. Before we combine hyperthermia with 

other standard medical therapies or immunotherapies such as vaccines, we need to know what’s going 

on mechanistically.”

Early results from their study looking at colon 

tumor models in mice showed that the antitumor 

effect of whole-body hyperthermia correlated with 

and enhanced granulocyte or neutrophil infiltrate in 

the tumors. “If you depleted the neutrophils or the 

granulocytes, you would lose the antitumor effect 

of whole-body hyperthermia,” explained Ostberg. 

Their results, published in 2005 in Immunological 

Investigations, showed not only an increased number 

of neutrophils at the tumor site but also increased 

activation of those cells. 

Additional studies awaiting publication will 

further examine the effects of fever-range hyperthermia on neutrophil migration, including the 

adhesion molecules involved in this process, as well 

as the effects of mild thermal stress on the activation 

phenotype of these cells.

An advantage of hyperthermia as a complementary or adjunctive treatment is its familiarity, 

Ostberg noted. “Patients understand it, because 

everyone understands or is familiar with the concept 

of fever.”

46
NCI Research in Complementary and Alternative Medicine

Many researchers are investigating vitamin 

D as a potential treatment for cancer. When converted into its active form, vitamin D promotes the 

differentiation of cells or inhibits the growth of 

cells, and preclinical studies suggest that it might 

help prevent metastasis. Analogues of the vitamin 

D hormone are being developed and tested in animal models of cancer. 

To learn about the mechanisms by which 

vitamin D analogues might achieve their effects, 

researchers at the University of Texas Medical 

Branch (UTMB) in Galveston are investigating 

parathyroid hormone-related protein (PTHrP), 

a growth factor produced by prostate cancer cells. 

Excess amounts of this protein increase the survival, 

growth, and migration of prostate cancer cells. 

 The researchers have recently shown that 

giving vitamin D analogues to mice with prostate 

tumors decreases levels of PTHrP, and this, in turn, 

reduces the size of tumors and the cancer’s spread 

to bone. 

“The rate of the tumor growth goes down, and 

you see a dramatic difference in both the size of the 

tumor and the incidence of metastasis,” said lead 

researcher Miriam A. Falzon, Ph.D. Her team is 

now trying to dissect the process by which vitamin 

D analogues alter PTHrP levels. 

With funding from NCI’s Division of Cancer 

Biology, the UTMB researchers are using mice to 

study the relationship among PTHrP, vitamin D, 

and the integrin α6β4, a messenger protein that 

may mediate the tumor effects of PTHrP and the 

antitumor effects of vitamin D. 

A recent finding in mice that may be relevant 

to humans, published in the February 2006 issue 

of Steroids, was the discovery that prostate cancer 

cells are less responsive to vitamin D if the cells 

no longer responded to androgen. In the human 

disease, prostate cancer cells progress from being 

androgen-responsive to androgen-unresponsive. 

“The results suggest that it may be critical to start 

treatment with these vitamin D compounds at an 

early stage, because if you wait too long then the cells 

might not respond to vitamin D,” Falzon noted. 

The researchers are also testing these compounds against breast cancer, and many effects 

observed in prostate cancer have been detected 

in breast cancer. Falzon predicted that promising 

vitamin D compounds will be used in combination 

with other drugs to treat cancer. 

“These compounds tend to have much milder 

side effects than other chemotherapeutic agents, 

and we think they are underutilized,” she said. 

“They have a range of anticancer effects.” 

Developing Effective and Efficient Treatments 

Testing the Effects of Vitamin D 

on Prostate Cancer in Mice 

Division of Cancer Biology

47
NCI CAM Annual Report 2005

For centuries, the Chinese have used an herb 

called Tripterygium Wilfordii Hook F to treat rheumatoid arthritis and other autoimmune diseases. 

Tripterygium Wilfordii Hook F, a vine-like member 

of the Celastraceae plant family, is known in China 

as Lei-Gong-Teng. The name, when translated, 

means the “thunder god” vine. The herb is being 

investigated in the United States as an agent to 

improve the outcomes of organ transplantation. It 

may also have anticancer properties, and researchers 

have been investigating the plant to identify derivative compounds that may be clinically useful. 

One such compound is called triptolide that 

studies have shown may prevent graft-versus-hostdisease and other conditions. Although triptolide 

clearly possesses immunosuppressive activity and 

has potential as a therapy, the mechanism of its 

action has not been clear. 

To address this question, Xin Chen, Ph.D., of 

the National Cancer Institute-Frederick and his 

colleagues tested the hypothesis that triptolide acts 

on dendritic cells, which play a critical role in the 

body’s immune response. They found that triptolide 

does inhibit some of the key functions of dendritic 

cells, including their maturation and migration, 

according to findings published in the October 1, 

2005 issue of the journal Blood. 

Developing Effective and Efficient Treatments 

Chinese Herbal Extract Shows Promise 

for Treating Immune Disorders 

Center for Cancer Research

The researchers say that because dendritic cells 

are involved in inflammation and autoimmune diseases, triptolide or herbal products containing this 

compound may be useful in the treatment of a range 

of disorders. “More research may yield a ‘conventional’ therapeutic agent—not just an alternative 

and complementary remedy—for a broad spectrum 

of diseases requiring immunosuppressive therapy,” 

said Chen. 

Some evidence suggests that triptolide may also 

promote the death of tumor cells and therefore may 

have potential as a cancer treatment. The researchers point out, however, that dendritic cells are also 

critical in initiating the antitumor response, and 

triptolide may block the process. 

“This potential adverse effect of triptolide 

should be taken into account and may negate the 

compound’s antitumor effects,” said Chen, who was 

trained in traditional Chinese medicine. He holds a 

C.M.D., which means Chinese medical doctor, and 

has been investigating the medicinal properties of 

traditional herbs at NCI-Frederick since 1999. 

48
NCI Research in Complementary and Alternative Medicine

Improving the Quality

of Cancer Care

As interventions and technologies become more sophisticated, 

the cancer community must build upon research evidence to 

continually enhance the quality, safety, and appropriateness of 

care. We are working for the consistent and equitable delivery 

of the full range of evidence-based interventions that are safe, 

patient-centered, effective, timely, efficient, and equitable. 

49
NCI CAM Annual Report 2005

Women with early breast cancer now have more 

and better treatment options than ever before, but 

understandably still struggle with fear, stress, and 

other negative psychological reactions to this frightening diagnosis. Besides negatively affecting quality 

of life, the mental stress that accompanies a diagnosis of cancer can actually contribute to suppression 

of the immune system, aggravating the side effects 

of chemotherapy and slowing the healing process.

Stress triggers an endocrine cascade beginning in the limbic system, the brain’s emotional 

center. This in turn triggers the pituitary gland to 

stimulate the adrenal gland to secrete cortisol, a 

hormone involved in regulating blood sugar levels 

and a known immunosuppressant. Nancy McCain, 

D.S.N., R.N., professor of Nursing at Virginia 

Commonwealth University, is leading a randomized trial to test if this pathway can be modulated by 

mind-body interventions that help patients manage 

their stress. “We think that anything that changes 

perceptions related to stress or changes the ability 

to deal with stress can have positive effects on the 

immune system,” explained McCain.

The investigators plan to enroll into the study 

approximately 240 women who are receiving chemotherapy for early breast cancer. After collection 

of blood and urine samples for measurement of 

immune and neuroendocrine biomarkers, women 

will be randomly assigned to one of two intervention groups designed to reduce stress—a tai chi 

group or a spiritual growth group—or to a control 

group receiving standard care. The intervention 

groups will begin 1 to 3 weeks after enrollment, and 

will meet once a week for 10 weeks. The investigators will collect physiological and psychological data 

at the end of the intervention and during two years 

of follow-up visits.

Pilot studies of both interventions in women 

with breast cancer and patients living with the 

AIDS virus showed positive improvements in quality of life and overall mood. If a positive correlation 

is found between the interventions and immune 

function, mind-body stress management strategies 

may provide important complementary therapy that 

can enhance not only psychosocial well-being and 

quality of life, but also the physical health of cancer 

patients, McCain said.

Improving the Quality of Cancer Care 

Stress Management and the Immune 

Response in Breast Cancer Patients

Division of Cancer Control and Population Sciences

50
T a i - C h i is being studied as one activity that 

can manage stress and increase immune function.

51
NCI CAM Annual Report 2005

An NCI-funded study of massage therapy or 

guided meditation to ease suffering for patients in 

hospice care—in conjunction with standard treatments—is testing the feasibility of using complementary and alternative medicine (CAM) interventions for end-of-life care. 

Investigators from the University of Washington School of Public Health and Community 

Medicine (UWSPHCM) identified the need for 

a randomized clinical trial to rigorously evaluate promising CAM therapies for this group of 

hospice patients. “A fundamental issue is that endof-life care for patients in the United States is 

substandard, if you’re looking at ‘comfort care’,” 

said UWSPHCM Associate Professor William 

Lafferty, M.D., principal investigator of the study. 

“Anytime end-of-life care has been studied or 

rated, almost 60 percent of people described their 

experience of having a loved one die in traditional 

medical settings as, at best, either fair or poor. That 

is a pretty low patient satisfaction level for something that we’re all going to face.”

 The study began in 2003 and has accrued 

more than 100 patients. Any patient in hospice 

care was eligible and approximately 70 percent of 

enrollees had cancer, Lafferty reported. Patients 

were randomized to one of three groups: massage, 

guided meditation, or a control group that received 

visits by hospice volunteers without either of the 

interventions. All CAM care was delivered by Bastyr University, a naturopathic medical school, using 

licensed alternative providers. 

The investigators are now analyzing data from 

about 3,000 patient visits. Outcomes measured 

include physical and depressive symptoms, mood, 

quality of life, and functional status. The patients’ 

families were administered a questionnaire on 

the quality of dying and death (QODD), which 

measures factors associated with more comfortable 

and peaceful deaths. Results from the study are 

expected to be available in 2007.

“The philosophy behind this study is that quality of life is just as important at the end of life as it 

is at earlier stages,” explained Lafferty. “Therefore, 

getting high-quality and effective medical care at 

the end of life is extremely important, and we think 

less technological methods of doing that through 

human touch and meditation will eventually play 

a greater role in improving comfort for people as 

they’re dying.”

“If you made the final transition for people 

more holistic at home, it might lead to fewer hospitalizations at the end of life,” he added. “Fewer 

hospitalizations, a better mental state at the end of 

life, an easier passing, a less arduous death—those 

are all the types of things we’re trying to measure 

and improve.”

Improving the Quality of Cancer Care 

Complementary and Alternative 

“Comfort Care” at the End of Life

Division of Cancer Prevention

52
NCI Research in Complementary and Alternative Medicine

Cancer patients undergoing autologous stem 

cell transplantation (ASCT) experience considerable 

stress and side effects from this aggressive treatment 

resulting in greatly impaired quality of life (QoL). In 

a bid to relieve those stresses and improve patients’ 

lives, researchers at the University of Virginia (UVA) 

Center for the Study of Complementary and Alternative Therapies and Cancer Center Stem Cell 

Transplant Unit are testing a novel massage therapy 

intervention with the potential to improve QoL and 

reduce treatment-related morbidity of persons with 

cancer undergoing ASCT. 

“Preliminary research suggests that adjunctive 

massage therapy may improve adverse symptoms 

and QoL of patients during treatment for cancer,” 

noted Principal Investigator Ann Gill Taylor, R.N., 

M.S., Ed.D. “Unfortunately, few controlled studies of massage interventions have been conducted 

among persons with cancer, and most studies have 

only evaluated immediate within-subject changes 

across a few brief massage sessions.”

Taylor, who is director of UVA’s Center for the 

Study of Complementary and Alternative Therapies, 

and her colleagues are testing a 7-week massage 

therapy intervention (three 50-minute massages 

per week) encompassing both the inpatient and 

outpatient phases of ASCT treatment. The intervention includes in-home massages when patients 

are resting at home and focused on their personal 

affairs. “This novel aspect of the intervention has 

the potential to provide continuity of care during 

the outpatient phases of ASCT, while minimizing 

treatment barriers and unnecessary patient burdens 

(e.g., travel),” added Taylor.

The researchers will evaluate the impact of the 

massage treatments by measuring of QoL, treatment-related symptoms (e.g., anxiety, stress, depression, pain, fatigue, nausea), short-term heart rate 

variability (HF-HRV), medication consumption 

(e.g., antiemetics), and perceived social support. 

Patients receiving the massages will be compared 

to a control group receiving standard medical care 

for ASCT.

Although the study is not complete, responses 

from the initial group of patients and family members have been very positive, Taylor reported. In 

one case, a patient who had experienced respiratory 

problems—unrelated to the study protocol—had to 

be intubated and transferred into one of the intensive 

care units for 24 hours. “The first request from this 

study participant immediately upon having his tube 

removed was ‘May I have one of my massages now?’” 

recalled Taylor. “I think this speaks for itself!”

Improving the Quality of Cancer Care 

Massage May Enhance Quality of Life 

in Stem Cell Transplant Patients

Division of Cancer Prevention

53
NCI CAM Annual Report 2005

Improving the Quality of Life

for Cancer Patients, Survivors,

and Their Families

Advances in our ability to detect, treat, and support cancer 

patients have turned this disease into one that is chronic, or readily 

managed, for many and curable for increasing numbers. While the 

ultimate goal of eliminating cancer altogether continues to be our 

long-term commitment, the capacity to dramatically reduce the 

suffering caused by cancer is within our immediate grasp. 

54
NCI Research in Complementary and Alternative Medicine

Nausea and vomiting remain significant problems for patients undergoing cancer chemotherapy 

treatments, despite new anti-nausea (antiemetic) 

medications available to treat these unpleasant side 

effects. Researchers are looking into the Traditional 

Chinese Medicine (TCM) practice of acupressure 

as an “added value” approach to help relieve these 

problems.

To test this approach, Suzanne L. Dibble, 

D.N.Sc., R.N., professor at the University of California, San Francisco, conducted a pilot study with 

“absolutely marvelous results that we published.” 

She then gained NCI funding for a larger, multicenter clinical trial with 160 breast cancer patients 

who were undergoing chemotherapy. 

The patients were randomly assigned to one of 

the following treatment groups: authentic acupressure applied by the patient’s fingers to the neiguan

point located above the wrist on the inside of the 

forearm plus usual nausea care; or “sham” placebo 

acupressure plus usual nausea care; or standard nausea care. All patients received “antiemetics as ordered 

by their physicians,” Dibble noted. “A strength of 

this study is that it does not pit modern Western 

medicine and TCM against each other.”

During the one-month treatment period of 

the study, patients were monitored on a daily basis 

through the use of diaries. “Every morning after 

the chemotherapy, they would treat themselves, 

continue to treat themselves on an as needed basis, 

and then they’d keep track of how many times a day 

they did the acupressure, took medications, or used 

other techniques to manage their nausea” Dibble 

explained.

Dibble plans to conduct a follow-up study in 

a similar patient population using a Transcutaneous Electrical Nerve Stimulation (TENS) device 

instead of finger pressure to trigger the neiguan

point response. “The feedback we had from the 

women is that their fingernails got in the way when 

applying pressure,” and the TENS device might be 

an easier way to apply the treatment, she explained.

Improving the Quality of Life for Cancer Patients, Survivors, and Their Families 

Acupressure Used to Treat Nausea 

From Chemotherapy

Division of Cancer Prevention

A c u p r e s s u r e . Researchers are looking 

into the Traditional Chinese Medicine 

(TCM) practice of acupressure as an “added 

value” approach to help relieve these problems.

55
NCI CAM Annual Report 2005

Breast cancer is the most common cancer among 

women in the United States and the toxic effects of 

chemotherapy and other treatments have been a 

primary spur to the increasing importance of—and 

attention by patients, clinicians, and researchers 

to—patients’ quality of life (QoL). 

In a pilot study among patients at the West 

Michigan Cancer Center in Kalamazoo, researchers found that women with breast cancer expressed 

the most interest in complementary and alternative 

medicine (CAM). The researchers also learned that 

reflexology—a specialized foot massage therapy—

was the intervention most likely to be chosen and 

maintained by such patients.

“We know patients are seeking such treatments, 

so the CAM field needs to establish the science 

behind the practice,” said Principal Investigator 

Gwen K. Wyatt, RN, Ph.D., at Michigan State 

University. Given the strong interest in reflexology, 

the question then becomes “what is the measurable 

impact of a consistently delivered therapeutic intervention, as measured by established and relevant 

QoL scales?” she added. Ryan and her colleagues 

will try to answer that question in a Phase III study 

of some 340 women with advanced (stages III or 

IV) breast cancer. 

Reflexology is an intricate procedure oriented 

around specific pressure points in the human foot. 

The third of patients in the study with the reflexology intervention will experience “the good hurt,” as 

Wyatt puts it. “The therapist exerts deep pressure 

with the thumb and then does a very specific movement known as the caterpillar crawl,” which is supposed to trigger an autonomic nervous system reflex 

relaxation response, as well as enhancing lymphatic 

drainage and flow.

Another third of patients will serve as controls 

and receive only conventional medical care. However, 

it is the final one-third group of patients that Wyatt 

is most excited about. “You could call them a placebo 

group,” she explained. “Current CAM research is 

beginning to emphasize the ‘active ingredient.’ With 

herbal medicines, for example, meaningful research 

tries to distinguish which chemical component of the 

treatment is responsible for the outcome.” Her placebo group will get a foot massage, but one designed 

to avoid the crucial pressure points.

In addition to the primary QoL scale (The 

FACT-G), her team will also try to isolate which 

“intervening variables” might be correlated with 

patient QoL outcomes. They will also recruit heavily 

in the African American communities of Detroit, 

Flint, and Saginaw Bay City, to reflect the fact that 

many advanced breast cancer patients come from 

that minority group.

Improving the Quality of Life for Cancer Patients, Survivors, and Their Families 

Foot Reflexology May Enhance Quality 

of Life in Breast Cancer Patients

Division of Cancer Prevention

56
NCI Research in Complementary and Alternative Medicine

Hot flashes associated with treatment-induced 

menopause in breast cancer survivors can cause 

discomfort, depression, insomnia, and anxiety, and 

otherwise negatively affect quality of life for those 

former patients. Hormone-replacement therapy 

relieves many symptoms of menopause but also 

increases the risk of breast cancer and cardiovascular problems. Other medications used to treat 

hot flashes can produce unwelcome side effects in 

many patients.

Consequently, researchers are looking for 

effective nonpharmacologic treatments for hot 

flashes in breast cancer patients and others. Gary 

Elkins, Ph.D., and his team from Scott and White 

Hospital in Temple, Texas recently completed an 

NCI-funded randomized trial of hypnosis for the 

treatment of hot flashes in breast cancer survivors. 

Hypnotherapy, which has been used successfully 

to treat cancer pain, uses the relaxation response, 

mental imagery, and power of suggestion to alter a 

person’s perception of their physiologic state. 

After a promising 16-person pilot study on hot 

flash symptoms, Elkins and colleagues expanded 

their research to a 60-person randomized trial. 

Breast cancer survivors experiencing an average 

of 10 hot flashes a day were randomly assigned 

either to 5 weeks of weekly hypnotherapy sessions, 

including training on self-hypnosis, or to a waitlist control group. 

Preliminary findings indicated that women in 

the hypnotherapy group had a 60 percent reduction 

in the frequency of hot flashes and a 69 percent 

decrease in the severity of their remaining hot 

flashes, Elkins noted. Women in the hypnotherapy 

group also reported improvements in sleep and 

mood. No changes were observed in women in the 

control group. 

Elkins and his team are now planning a larger, 

multicenter trial to confirm and clarify their data. 

The expanded study will use a “structured attention” control group, in which women in the control 

group receive therapy sessions that do not include 

hypnosis. In addition, data will be collected to analyze whether the reduction in perceived hot flashes 

is due to physiologic effects or/and psychological 

responses such as expectancies and hypnotizability 

of study participants.

Elkins has found that patients are very interested in participating in these studies. “The basic 

philosophy that underlies hypnotic treatment is, 

‘empower the patient,’” he explained. “It’s not so 

much something that’s done to the patient as a collaborative relationship between doctor and patient 

in which the patient learns hypnotic techniques 

and how to utilize self-hypnosis toward achieving 

better control over her own body.” 

Improving the Quality of Life for Cancer Patients, Survivors, and Their Families 

Hypnotherapy Eases Hot Flashes 

in Breast Cancer Survivors

Division of Cancer Control and Population Sciences

57
NCI CAM Annual Report 2005

Overcoming Cancer 

Health Disparities

Overcoming cancer health disparities is a critical component 

of each of the research areas described in this Annual Report. 

Minorities and other underserved populations variously 

distinguished by race, ethnicity, gender, age, socioeconomic 

status, geographic location, occupation, and education bear a 

far greater cancer burden than the general population. 

58
NCI Research in Complementary and Alternative Medicine

NCI staff are using data from the California 

Health Interview Survey (CHIS) of over 9,000 

consumers to examine the use of complementary 

and alternative medicine (CAM) in preventing and 

treating cancer and other chronic illnesses, including 

among medically underserved minority groups. 

CHIS-CAM is a collaborative effort of NCI 

and the University of California, Los Angeles and 

is the one of the largest population-based surveys 

conducted to date to document the use of CAM by 

people who have had cancer diagnoses. California’s 

population includes many Asians, Latin Americans, and African Americans, so the study benefits 

from large samples of these groups. It is based on 

telephone interviews in 2003 among a sample of 

California adults regarding their use during the past 

12 months of CAM providers (e.g.., chiropractors, 

acupuncturists), special diets, dietary supplements, 

mind-body methods (e.g., yoga, meditation), selfprayer, and support groups.

The findings, published in the medical journal Evidence-Based Complementary and Alternative 

Medicine, counter the widely held assumption that 

whites are more likely to use CAM approaches than 

other ethnic groups. 

“For example, Asian/Pacific Islanders have the 

highest use of acupuncture and Traditional Chinese Medicine (TCM), and African Americans are 

most likely to report praying for their health,” the 

researchers noted. “In other instances, the differences between whites and other groups are minimal. 

Latinos consistently report a lower level of use than 

whites and other racial/ethnic groups on every measure of CAM utilization except self-directed prayer, 

where they report more use than any other group 

except for African Americans.”

Overall, the use of CAM by California consumers was found to be substantial. A quarter of the 

9,187 respondents reported seeing a CAM provider 

in the past 12 months and even higher numbers 

reported using other CAM methods, including 

dietary therapy (41 percent) and two or more dietary 

supplements (62 percent). 

Among the 1,844 survey respondents who 

reported a diagnosis of cancer, use of CAM providers 

and other methods were not distinctly different than 

for people diagnosed with other chronic illnesses. 

“However, those in the cancer group are considerably less apt (36.1 percent versus 48.3 percent) to 

report employing dietary therapies and more apt to 

report self-directed prayer (58.4 percent versus 49.9 

percent) and attending support groups (11.3 percent versus 7.9 percent),” the researchers reported. 

“These patterns may be due to the use of CAM to 

ameliorate the psychological distress that is typically 

associated with a diagnosis of cancer.”

Overcoming Cancer Health Disparities 

CAM Survey of California Consumers 

Includes Underserved Minority Groups

Division of Cancer Control and Population Sciences

59
NCI Scientists Spearhead 

Pioneering Research on CAM

To the public, NCI is often thought of in terms of being the largest supporter of cancer research in the United States and the 

world. That is clearly one of NCI’s most important functions. Perhaps the untold story, however, is the outstanding research 

being carried out by the talented scientists and clinicians in the Institute’s own laboratories or intramural programs within 

NCI’s Center for Cancer Research (CCR) and the Division of Cancer Epidemiology and Genetics (DCEG). 

NCI’s intramural researchers perform essential basic, clinical, and epidemiologic research, upon which a great deal of research 

by outside institutions or extramural programs are eventually based. This principle certainly applies to the area of CAM research 

where CCR and DCEG scientists are engaged in exciting and pioneering research that is both high risk and high impact. The 

intramural program also serves as the training ground for thousands of investigators launching their careers in science. 
NCI Research in Complementary and Alternative Medicine

When Joost J. Oppenheim, M.D., was introduced to clinical oncology research at NCI more 

than 40 years ago, he came away convinced that 

more research was needed to understand how the 

body’s own natural defense mechanisms could be 

harnessed to cope with cancer. This objective lead 

to a career focused on endogenous immune system 

regulatory proteins, cytokines, and chemokines.

Today, as head of the Laboratory of Molecular 

Immunoregulation at NCI-Frederick, Oppenheim’s projects include an effort to identify components of natural products and Traditional Chinese 

Medicines (TCM) that act on proteins known as 

chemokines or chemoattractant cytokines. Chemokines play a central role in coordinating the 

body’s natural defenses by recruiting immune cells 

from the blood to the sites of inflammation. Some 

chemokines also play a role in fetal development, 

tumor growth, and the growth of new blood vessels 

that feed tumors, also called angiogenesis. 

A goal of the project is to identify both plant and 

animal components of TCM compounds that might 

inhibit chemokines or chemokine receptors. The 

hypothesis supporting this goal is that inhibitors of 

chemokine-induced cell migration are likely to have 

anti-inflammatory, anti-angiogenic and anti-tumor 

activities. “It could potentially be very useful to have 

inhibitors of the chemokines and the chemokine 

receptors that mobilize cells and promote angiogenesis and metastases,” Oppenheim explained, noting 

that inhibitors of chemokines can reduce the spread 

of tumors in some animal models. 

Since 1999, these efforts have been carried out 

in conjunction with Oppenheim’s NCI colleagues 

O. M. Zack Howard, Ph.D., and Xin Chen, M.D., 

Ph.D. Their efforts have identified several discrete 

chemicals that inhibit chemoattractant receptors. 

These include shikonin which blocks ligand binding to CCR1 and most other chemokine receptor 

intracellular signaling and ursodeoxycholic acid 

that blocks ligand binding to the fMLP receptors. 

These compounds are currently being evaluated in 

preclinical models as single anti-tumor agents. 

Further, two TCM compounds—called Qiu 

Kai Ling and Shuang Huang Lian—have been 

shown to inhibit the function of the canonical regulator of inflammation, NFkB, and subsequently 

to suppress chemokine and chemokine receptor 

expression. Future studies will evaluate the ability 

of these compounds to inhibit inflammation associated with tumor growth and angiogenesis.

Currently, these NCI researchers are trying to 

identify agents in TCM that could promote the 

body’s immune response by stimulating antigenpresenting cells and suppressing T-regulatory cells. 

This would expand the targets beyond chemokines 

and chemokine receptors to more general regulators of the tumor immune system.

NCI Scientists Spearhead Pioneering Research on CAM 

Testing Traditional Chinese Medicines 

for Anti-Cancer Agents 

Center for Cancer Research 

61
NCI CAM Annual Report 2005

Many phytochemicals—compounds found naturally in plants—have been shown to have preventative effects in animal models of cancer development. 

In addition, epidemiologic studies have suggested 

that diets rich in phytochemicals from fruits and 

vegetables may prevent or slow the development of 

certain tumor types. Phytochemicals of great interest to cancer-prevention researchers include: diosmin, from citrus fruit; kaempferol, found in leafy 

green vegetables; and resveratrol, present in grapes 

and red wine.

Since 1999, the laboratory of Grace Yeh, Ph.D., 

in NCI’s Center for Cancer Research, has examined 

how these and other phytochemicals can protect 

cells against DNA damage caused by external carcinogens, possibly preventing the development of 

cancer. Their main focus has been on understanding 

the biochemical and molecular mechanisms responsible for the protective effect of phytochemicals and 

other chemopreventive agents against aryl hydrocarbon-induced carcinogenesis. 

The aryl hydrocarbon receptor (AhR) is a cytosolic protein found inside the cells that mediates 

several important signaling pathways. When a carcinogen binds to AhR, it triggers a signaling cascade 

that leads to production of the enzyme cytochrome 

P450 1A1 (CYP1A1), which then activates the carcinogen into a form that can cause genetic damage. 

AhR also controls other genes that affect both the 

activation and detoxification of carcinogens. 

Carcinogens under study in the Yeh laboratory include benzo[a]pyrene, a carcinogen found 

in cooked meat, cigarettes, and industrial waste, 

and members of the dioxin family of toxins. In a 

comprehensive study of all commercially available 

purified phytochemicals, Yeh and her colleagues 

found that the flavonoid and curcuminoid classes of 

phytochemicals bind to the AhR and modulate the 

cell’s capacity to activate aryl hydrocarbons, thereby 

modifying the cellular response to environmental 

carcinogens. Yeh’s lab also identified resveratrol as 

the first and only known pure antagonist of the 

AhR. Resveratrol blocks the activation of the AhR 

by carcinogens and inhibits CYP1A1 expression.

Other related work from the Yeh laboratory 

has examined the chemoprotective effects of Traditional Chinese Medicine (TCM) compounds and 

of salicylic acid, which was initially obtained from 

the bark of the willow tree. The investigators are 

now moving promising results from their laboratory 

experiments into animal studies. One study is looking at the ability of phytochemicals and other chemopreventive agents to prevent carcinogen-induced 

lung and breast cancers in rodents. 

Other animal studies are examining the gender 

differences in lung cancer to investigate whether 

any chemopreventative benefit derived from phytochemicals differs between males and females. 

Because some phytochemicals have a weak hormonal 

effect, “one phytochemical may be more effective in 

one gender than another,” Yeh explained.

NCI Scientists Spearhead Pioneering Research on CAM 

Plant Compounds Protect Cells from 

Carcinogen-Induced Damage

Center for Cancer Research

62
D i o s m i n , found in the skin of lemons, is being 

studied by cancer prevention researchers.

63
D r y B e a n s . In one study, participants who tripled their intake of dry beans 

(legumes) had a 65 percent reduction in risk of advanced adenoma recurrence.

64
NCI Research in Complementary and Alternative Medicine

A large, 4-year clinical trial conducted during the 1990s found no benefit from a high fiber, 

low-fat, fruits, and vegetable diet for lowering the 

risk of recurring colorectal polyps (adenomas), the 

main precursor lesion of colorectal cancer (CRC). 

However, NCI scientists recently found in a post 

analysis of the data from the Polyp Prevention Trial 

(PPT) that participants who tripled their intake of 

dry beans (legumes) had a 65 percent reduction in 

risk of advanced adenoma recurrence—adenomas 

most likely to progress to colorectal cancer, reported 

Elaine Lanza, Ph.D., head of NCI’s Colon Cancer 

Prevention Group within the Center for Cancer 

Research (CCR). These findings were published in 

the July 2006 issue of Journal of Nutrition. 

Based on her analysis of the PPT data, Lanza 

has begun a feeding study using a legume-enriched, 

low glycemic (blood sugar) diet among men who are 

at increased risk for colorectal cancer because they 

have already had at least one polyp removed or are 

insulin-resistant—a condition that often leads to 

type 2 diabetes. 

“Both colorectal cancer and insulin resistance 

are increasingly recognized as chronic, low-level 

inflammatory conditions,” explained Lanza whose 

colon cancer group is part of the CCR Laboratory 

of Cancer Prevention. “Therefore, we are looking for 

biomarkers of inflammation in the men which are 

related to colorectal cancer and we are also measuring the effect of diet on changes in gene expression 

by looking at changes in messenger RNA from 

colon cells sloughed off into the feces.” NCI has 

already begun enrolling the 68 men for the study. 

Lanza expects to have results by mid-2007. 

If the high legume diet shows a beneficial 

impact on biomarkers of CRC risk, a larger clinical 

trial could be conducted to test whether dry beans 

lowers the risk of recurrence of advanced adenomas. 

Lanza believes that the combination of a dietary 

intervention, plus a pharmaceutical agent—such 

as aspirin, a well known anti-inflammatory drug—

might be the most successful strategy for preventing colorectal cancer. “Drugs have numerous side 

effects,” she noted. “If you could have the right diet, 

you could hopefully, reduce the dose of the drug you 

might need for cancer prevention.”

NCI Scientists Spearhead Pioneering Research on CAM 

Impact of Legume (Dry Beans) Diet 

on Colorectal Cancer Risk Studied

Center for Cancer Research

65
NCI CAM Annual Report 2005

NCI’s Nutritional Epidemiology Branch 

(NEB) has for many years pursued investigations 

into the impact of diet, nutrition, and physical activity on the risk of cancer.

“Our primary objective is to clarify the relationship between what we eat—and other nutritionrelated activities and exposures—and the development of and also the prognosis for a variety of 

cancers,” explained NEB Chief Arthur Schatzkin, M.D., Dr.P.H. “In the last few years there has 

been a particular emphasis on ‘energy balance’—the 

dynamic interplay of energy intake and physical 

activity that is reflected in body fatness—as an 

important risk factor for a number of cancers.”

The Branch, which is part of NCI’s Division 

of Cancer Epidemiology and Genetics (DCEG), 

has been involved in a number of major, pioneering 

studies into nutritional interventions, such as the 

Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted in Finland. “One of 

the unexpected but important findings in that study 

was a reduced incidence of prostate cancer among 

men who took vitamin E,” Schatzkin recalled. 

Other major studies with NEB involvement 

include the Polyp Prevention Trial (PPT) (see related 

article on page 65), an investigation of the effect of 

a low fat, high fiber, fruit- and vegetable-enhanced 

dietary pattern on the recurrence of colorectal adenomas (invasive cancer precursor lesions), and the 

ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT). NEB also led an analysis 

using data from the Prostate, Lung, Colorectal, 

and Ovarian Cancer Screening Trial (PLCO) that 

showed a protective association between dietary 

fiber intake and colorectal adenomas. 

NEB scientists are also leading the massive NIHAARP Diet & Health Study. “This is the largest indepth prospective cohort study of diet and cancer 

ever done, involving over 566,000 men and women,” 

noted Schatzkin. “We went into the field in 1995–96 

with the goal of looking at the nutritional and other 

lifestyle factors that are associated with cancer. This 

study was designed to include people at both high 

and low levels of intake of various foods and nutrients 

to make good biological comparisons.”

Important findings from the NIH-AARP 

study have been submitted to be published. Schatzkin says these will include new discoveries on the 

role of being overweight or obese on risk of death 

and cancer.

NEB has also been on the forefront of developing methods for accurately measuring what people 

eat, including consumption of meat in its various 

forms. “There are a lot of concerns that many of the 

instruments nutritional epidemiologists used in past 

are somewhat inaccurate,” Schatzkin commented. 

“That could cause us to miss relationships between 

diet and cancer that are important and that just 

won’t show up if we use imprecise instruments.” 

For example, NEB has been collaborating with 

other NCI scientists involved in developing a webbased dietary “recall” survey tool for use by participants in nutrition studies. “It’s very user-friendly 

and may enable us to see some things that have been 

obscured, because our instruments haven’t been 

good enough,” he said.

NCI Scientists Spearhead Pioneering Research on CAM 

NCI’s Nutritional Epidemiology 

Branch Focuses on Impact of Diet 

and Activity on Cancer Risk

Division of Cancer Epidemiology and Genetics

66
NCI Research in Complementary and Alternative Medicine

Cancer rates can vary dramatically around the 

world and researchers often develop insights about 

risk factors for certain cancers by looking closely 

at populations with higher than average rates of 

those diseases. The rural county of Linxian in north 

central China, for example, has some of the world’s 

highest cancer rates and more than 85 percent of 

those cancers occur in the esophagus and the upper 

stomach (gastric cardia).

For more than two decades, NCI scientists 

have been collaborating with their Chinese counterparts to examine and interrupt these disease 

patterns. After preliminary work, two major clinical trials were designed—collectively known as the 

Nutrition Intervention Trials—based on the “historical fact that the Linxian population has a diet 

deficient in several nutrients we have linked to cancer of the esophagus and gastric cardia,” explained 

Philip R. Taylor, M.D., Sc.D, a senior investigator 

with NCI’s Division of Cancer Epidemiology and 

Genetics (DCEG).

In 1986, the General Population Trial enrolled 

nearly 30,000 people between the ages of 40 and 69 

living in Linxian, and began to test four different 

vitamin/mineral combinations. After 5 years, participants who took a daily supplement of selenium, 

vitamin E, and beta-carotene had a 9 percent drop in 

the overall risk of death. Their risk of cancer mortality was down 13 percent, although the intervention 

reduced esophageal cancer deaths by only 4 percent. 

The major impact was shown for sites located 

further along the digestive tract, with stomach cancer reduced by 21 percent overall, and by 28 percent 

in the lower non-cardia region (the body of the 

stomach). Cerebrovascular events (stroke) were the 

second-leading cause of death in Linxian, and these 

too were reduced by 10 percent in the group receiving the daily supplements.

“Those findings were meaningful,” said Taylor, 

“but what has happened since that time is perhaps 

even more interesting.” Investigators have continued to follow trial participants since they stopped 

supplementation in 1991. “Surprisingly, the reduced 

risks observed for persons who were supplemented 

with selenium, vitamin E, and beta-carotene during 

the trial have continued for up to 10 years. In short, 

the advantage in survival we found initially has persisted and actually increased.”

NCI’s partners in China are continuing this 

follow-up surveillance. You-Lin Qiao, M.D., 

Ph.D., who heads the Department of Epidemiology at the Cancer Institute, Chinese Academy of 

Medical Sciences, has done additional analyses of 

selenium levels in the blood from this same group 

of Chinese individuals. He and his colleagues were 

able to confirm that the mineral has a significant 

impact on the subsequent development of upper 

gastrointestinal cancers. They concluded that if 

selenium supplementation could be provided to 

high-risk populations—like the one at Linxian—it 

could have a strong protective effect against esophageal and gastric cardia cancers. Plans are now 

underway to fortify the salt in that region with 

selenium, Taylor reported.

NCI Scientists Spearhead Pioneering Research on CAM 

Selenium Studied for Prevention of 

Esophageal and Gastric Cancers

Division of Cancer Epidemiology and Genetics

67
NCI CAM Annual Report 2005

Gastric cancer—also referred to as stomach 

cancer—is second only to lung cancer as a cause of 

cancer deaths worldwide, though it is much less of a 

threat to public health in the United States than it 

is in developing countries. Gastric cancer incidence 

is disproportionately high in parts of China. For 

example, in the rural county of Linqu, gastric cancer 

accounts for 42 percent of cancer deaths.

To address this public health challenge, there 

have been a number of fruitful collaborations for 

more than two decades between NCI and scientists 

like Wei Cheng You, M.D., from the Beijing Institute for Cancer Research (BICR). You and researchers from NCI’s Division of Cancer Epidemiology 

and Genetics (DCEG), obtained valuable clues to 

gastric cancer causes and the factors affecting precancerous gastric conditions by examining Linqu 

villagers’ stomachs with endoscopes as part of a 

population-based screening study. 

This and other work in China provided a solid 

framework for a follow-up study for preventing 

gastric cancer using a combination of drugs, antibiotics, and dietary supplements—such as garlic compounds, multivitamins, and minerals, said Mitchell 

Gail, M.D., Ph. D., current chief of NCI’s Biostatistics Branch. 

When the researchers examined tiny biopsies 

taken from the Chinese villagers who had been 

screened, they found a startling and very clear map 

of the progression to gastric cancer, Gail noted. 

Nearly every individual examined had some form of 

gastric histopathology, ranging from mild lesions—

such as superficial gastritis—to dysplasia, which is a 

precursor to gastric cancer. Nearly 70 percent of the 

study population was infected with H. pylori bacteria 

which cause inflammation and stomach ulcers and 

represent a major risk factor for gastric cancer.

“We wanted to learn more about the causes of 

gastric cancer, and how we might make an impact 

in preventing the disease,” Gail explained. “In our 

follow-up clinical trial, we will tease out the impact 

of treating the H. pylori infection, as well as the 

separate and combined effects of a giving a garlic 

supplement and the combination of vitamins C 

and E and selenium, which earlier epidemiological studies suggested might be protective against 

gastric cancer.”

You, Gail, and their colleagues enrolled 3,411 

men and women into this prospective, randomized 

blinded trial in 1995. Those who were infected with 

H. pylori were randomly assigned to receive a placebo or treatment with amoxicillin and omeprozole. 

Those individuals who weren’t infected still got a 

placebo. After 3 months, all participants began taking pills that contained the garlic preparation, the 

vitamin/mineral combination, or placebo. Treatment continued for more than 7 years. Gastroscopy 

and gastric biopsies will permit the researchers to 

evaluate the various and combined impacts of the 

interventions on the actual progression of gastric 

disease in each patient.

The study’s findings were published in the September 2006 issue of the Journal of the National 

Cancer Institute.

NCI Scientists Spearhead Pioneering Research on CAM 

Preventive Study of Gastric Cancer 

Emerges from Collaboration with China

Division of Cancer Epidemiology and Genetics

68
NCI Research in Complementary and Alternative Medicine

Although prostate cancer is the most commonly diagnosed cancer among men in the United 

States, the causes of most cases of the disease remain 

largely unexplained.

“We don’t really know much about the etiology 

of prostate cancer other than the factors of aging, 

race, and a family history of prostate cancer,” said 

Ann Hsing, Ph.D., a senior investigator with NCI’s 

Division of Cancer Epidemiology and Genetics 

(DCEG). While prevalence of latent, early-stage 

prostate cancer appears to be comparable around the 

world, clinical disease in western countries is 30 to 

50 times higher than in Asian men, she noted. This 

large difference in risk cannot be explained entirely 

by population differences in prostate cancer screening, which is much less common in Asian countries.

Hsing and her colleagues are investigating this 

remarkable epidemiological pattern in the NCIShanghai Collaborative Prostate Cancer Study. The 

study, which began in the 1990s, was the first population-based interdisciplinary study in men who are 

at low risk for prostate cancer. 

Working closely with the Shanghai Cancer 

Institute, the researchers identified 286 cases of prostate cancer and matched them with 471 randomly 

selected healthy controls. The data have provided 

several intriguing clues and the researchers have 

published more than two dozen papers exploring 

prostate cancer risk factors. In general, the study’s 

results indicate that both lifestyle and nutritional factors 

contribute to the disease.

Asian men are generally 

very lean compared to American men. Their diet also differs, and as a consequence, so 

too does their propensity for 

developing insulin-resistance. 

They found that prostate cancer risk is greater among those with higher levels of 

education, a higher waist-to-hip ratio (an indicator 

for abdominal obesity), and a higher intake of total 

calories, red meat, and animal fat and protein. Risk 

was found to decrease among those consuming more 

peppers, mushrooms, and allium vegetables—such 

as garlic and scallions.

Hsing thinks the data also support the likelihood that many of these measurable risks have an 

underlying hormonal and metabolic basis. Insulinresistant men have an elevated risk, while those who 

are sensitive to insulin have a reduced risk. High 

levels of IGF-1, an insulin-like growth factor, more 

than doubled the risk, while high levels of the insulin-like growth factor binding proteins IGFBP-3 

cut risk nearly in half. 

“Most of the lifestyle factors that seemed to 

confer risk in the study are closely linked to westernization,” said Hsing. The scientists are in the process 

of developing what they call a “westernization index” 

to represent these lifestyle factors, which they found 

highly correlated with an adverse metabolic profile. It would include higher serum levels of insulin, 

IGF-I, and androgens—biomarkers that have been 

previously implicated in prostate cancer. The population-based data from the landmark Shanghai study 

provide a potential biological mechanism linking 

westernization and increased prostate cancer rates.

NCI Scientists Spearhead Pioneering Research on CAM 

Lessons from China Could Enhance 

Prostate Cancer Prevention in the West

Division of Cancer Epidemiology and Genetics

T h e N C I - S h a n g h a i 

C o l l a b o r a t i v e P r o s t a t e 

C a n c e r S t u d y , which began in 

the 1990s, was the f irst population-based 

interdisciplinary study in men who are at 

low risk for prostate cancer.

C h i n a

69
NCI CAM Annual Report 2005

This is a selected list of some of the most important peer-reviewed scientific 

articles about the findings and analyses of NCI-supported CAM research studies 

published during FY 2005. The articles are classified and grouped according to 

research type: cancer prevention, cancer treatment, and cancer side effect/symptom 

management. Abstracts of the articles are available online through the National 

Library of Medicine’s “PubMed” database at www.pubmed.com.

Cancer Prevention

Baron JA, Beach M, Wallace K, Grau MV, Sandler 

RS, Mandel JS, Heber D, Greenberg ER. Risk of 

prostate cancer in a randomized clinical trial of 

calcium supplementation. Cancer Epidemiology, Biomarkers & Prevention, March 2005; 14(3):586–9.

Chen G, Heilbrun LK, Venkatramanamoorthy 

R, Maranci V, Redd JN, Klurfeld DM, Djuric Z. 

Effects of low-fat and/or high-fruit-and-vegetable 

diets on plasma levels of 8-isoprostane-F2alpha in 

the Nutrition and Breast Health study. Nutrition 

and Cancer, 2004;50(2):155–60.

Hedlund TE, Maroni PD, Ferucci PG, Dayton R, 

Barnes S, Jones K, Moore R, Ogden LG, Wahala 

K, Sackett HM, Gray KJ. Long-term dietary habits 

affect soy isoflavone metabolism and accumulation in prostatic fluid in Caucasian men. Journal of 

Nutrition, June 2005; 135(6):1400–6.

Henning SM, Niu Y, Lee NH, Thames GD, 

Minutti RR, Wang H, Go VL, Heber D. Bioavailability and antioxidant activity of tea flavanols after 

consumption of green tea, black tea, or a green tea 

extract supplement. American Journal of Clinical 

Nutrition, December 2004; 80(6):1558–64.

Hernandez BY, McDuffie K, Franke AA, Killeen 

J, Goodman MT. Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the 

cervix. Nutrition and Cancer, 2004; 49(2):109–24.

Kim H, Hall P, Smith M, Kirk M, Prasain JK, 

Barnes S, Grubbs C. Chemoprevention by grape 

seed extract and genistein in carcinogen-induced 

mammary cancer in rats is diet dependent. Journal of 

Nutrition, December 2004; 134(12 Suppl):3445S–

3452S.

Wu AH, Stanczyk FZ, Martinez C, Tseng CC, 

Hendrich S, Murphy P, Chaikittisilpa S, Stram 

DO, Pike MC. A controlled 2-month dietary fat 

reduction and soy food supplementation study in 

postmenopausal women. American Journal of Clinical 

Nutrition, May 2005; 81(5):1133–41.

Cancer Treatment

Adams KF, Lampe PD, Newton KM, Ylvisaker JT, 

Feld A, Myerson D, Emerson SS, White E, Potter 

JD, Lampe JW. Soy protein containing isoflavones 

does not decrease colorectal epithelial cell proliferation in a randomized controlled trial. American 

Journal of Clinical Nutrition, September 2005; 

82(3):620–6.

Scientific Publications

70
Constantinou AI, White BE, Tonetti D, Yang Y, 

Liang W, Li W, van Breemen RB. The soy isoflavone daidzein improves the capacity of tamoxifen 

to prevent mammary tumours. European Journal of 

Cancer, Epub Jan 18, 2005; 41(4):647–54.

Edwards IJ, Berquin IM, Sun H, O’Flaherty JT, 

Daniel LW, Thomas MJ, Rudel LL, Wykle RL, 

Chen YQ . Differential effects of delivery of 

omega-3 fatty acids to human cancer cells by lowdensity lipoproteins versus albumin. Clinical Cancer 

Research, December 15, 2004; 10(24):8275–83.

Frye RF, Fitzgerald SM, Lagattuta TF, Hruska 

MW, Egorin MJ. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clinical Pharmacology and Therapeutics, October 2004; 76(4):323–9.

Huang X, Chen S, Xu L, Liu Y, Deb DK, Platanias 

LC, Bergan RC. Genistein inhibits p38 map kinase 

activation, matrix metalloproteinase type 2, and cell 

invasion in human prostate epithelial cells. Cancer 

Research, April 15, 2005; 65(8):3470–8.

Katiyar SK, Roy AM, Baliga MS. Silymarin induces 

apoptosis primarily through a p53-dependent 

pathway involving Bcl-2/Bax, cytochrome c release, 

and caspase activation. Molecular Cancer Therapeutics, 

February 2005; 4(2):207–16.

Liu B, Edgerton S, Yang X, Kim A, Ordonez-Ercan 

D, Mason T, Alvarez K, McKimmey C, Liu N, 

Thor A. Low-dose dietary phytoestrogen abrogates 

tamoxifen-associated mammary tumor prevention. 

Cancer Research, February 1, 2005; 65(3):879–86.

Loprinzi CL, Levitt R, Barton DL, Sloan JA, 

Atherton PJ, Smith DJ, Dakhil SR, Moore DF Jr, 

Krook JE, Rowland KM Jr, Mazurczak MA, Berg 

AR, Kim GP; North Central Cancer Treatment 

Group. Evaluation of shark cartilage in patients 

with advanced cancer: a North Central Cancer Treatment Group trial. Cancer, July 1, 2005; 

104(1):176–82.

Mantena SK, Roy AM, Katiyar SK. Epigallocatechin-3-gallate inhibits photocarcinogenesis through 

inhibition of angiogenic factors and activation of 

CD8+ T cells in tumors. Photochemistry and Photobiology, September-October 2004; 81(5):1174–9.

Sartippour MR, Rao JY, Apple S, Wu D, Henning 

S, Wang H, Elashoff R, Rubio R, Heber D, Brooks 

MN. A pilot clinical study of short-term isoflavone 

supplements in breast cancer patients. Nutrition and 

Cancer, 2004; 49(1):59–65.

Seeram NP, Adams LS, Henning SM, Niu Y, 

Zhang Y, Nair MG, Heber D. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin 

extract are enhanced in combination with other 

polyphenols as found in pomegranate juice. Journal 

of Nutritional Biochemistry, June 2005; 16(6):360–7.

Sharma SD, Katiyar SK. Dietary grape-seed proanthocyanidin inhibition of ultraviolet B-induced 

immune suppression is associated with induction 

of IL-12. Carcinogenesis, Epub June 29, 2005; 

27(1):95–102.

Zi X, Simoneau AR. Flavokawain A, a novel 

chalcone from kava extract, induces apoptosis in 

bladder cancer cells by involvement of Bax proteindependent and mitochondria-dependent apoptotic 

pathway and suppresses tumor growth in mice. 

Cancer Research, April 15, 2005; 65(8):3479–86.

Cancer Side Effect/

Symptom Management

Mehendale S, Aung H, Wang A, Yin JJ, Wang CZ, 

Xie JT, Yuan CS. American ginseng berry extract 

and ginsenoside Re attenuate cisplatin-induced 

kaolin intake in rats. Cancer Chemotherapy and Pharmacology, Epub Mar 25, 2005; 56(1):63–9.

Mills PJ, Parker B, Dimsdale JE, Sadler GR, 

Ancoli-Israel S. The relationship between fatigue 

and quality of life and inflammation during 

anthracycline-based chemotherapy in breast cancer. 

Biological Psychology, April 2005; 69(1): 85–96.

Ostberg JR, Ertel BR, Lanphere JA. An important 

role for granulocytes in the thermal regulation of 

colon tumor growth. Immunological Investigations, 

2005; 34: 259–272.

Scientific Publications

71
NCI CAM Annual Report 2005 Appendix An NCI-sponsored clinical trial meets one or more of the following criteria: the protocol (1) has been reviewed and approved by NCI’s CTEP Protocol Review Committee or by an approved NCI-designated Cancer Center Protocol 

Review and Monitoring System and/or (2) receives support through an NCI grant, contract or cooperative agreement. 

PDQ Cancer CAM Clinical 

Trials Active in FY 2005 Primary ID

Type ofTrial

AgeRange

Sponsorof Trial Phase(s)

Pediatric TrialsRandomized Study of Electroacupuncture for Treatment of Delayed Chemotherapy-Induced Nausea and Vomiting in Patients With Newly Diagnosed Pediatric Sarcoma, Neuroblastoma, Nasopharyngeal Carcinoma, or Germ Cell Tumors

NCCAM-02-AT-0172

Supportive care 10 to 35 NCCAM; NCI No phase 

specified

Randomized Study of Traumeel® S for the Prevention and Treatment of Mucositis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

COG-ACCL0331 Supportive care 3 to 25 NCI No phase 

specified

Randomized Prospective Pilot Study of Acupressure in Preventing Chemotherapy-Associated Nausea and Vomiting in Pediatric Patients With Cancer

CCCWFU-02104 Supportive care 2 to 21 NCI No phase 

specified

Phase I Study of Beta-Glucan and Rituximab in Pediatric Patients With Relapsed or Progressive CD20-Positive Lymphoma or Leukemia or Post-Allogeneic Stem Cell Transplant-Related Lymphoproliferative Disorder

MSKCC-03095 Treatment Under 22 NCI Phase I

72
PDQ Cancer CAM Clinical 

Trials Active in FY 2005 Primary ID

Type ofTrial

AgeRange

Sponsorof Trial Phase(s)

Phase II Randomized Pilot Study of Silymarin (Milk Thistle Extract) in Patients With Acute Lymphoblastic Leukemia Receiving Hepatotoxic Chemotherapy

CPMC-IRB-14117 Supportive care 2 to 21 NCI Phase II

Adult TrialsChemoprevention Study of Broccoli Sprout Extract in Smokers

JHOC-J0427 Prevention Over 18 NCI No phase 

specified

Randomized Study of Dietary Modification Intervention Comprising Individual Counseling Versus Automated Computer-Based Counseling Versus Both Dietary Modification Interventions in Helping Healthy Women Adopt a Cancer Prevention Diet

KAISER-R01-CA098496

Prevention 30 to 70 NCI No phase 

specified

Randomized Study of Fish Oil Supplements in Preventing Prostate Cancer in Patients With Prostatic Intraepithelial Neoplasia or Who Are at Risk for Developing Prostate Cancer

OHSU-CPC04131-LX Prevention 18 and over NCI No phase specified

Study of Zinc Supplements for Reduction of Cadmium Levels in Smokers

CCCWFU-98903 Prevention; 

Biomarker/Laboratory analysis

21 and over

NCI No phase 

specified

Phase I Study of Inositol for the Prevention of Lung Cancer in Patients With Bronchial Epithelial Dysplasia Who Are Current or Former Smokers

BCCA-U98-0411 Prevention 40 to 74 NCI Phase I

Phase I Randomized Chemoprevention Study of Genistein in Healthy Postmenopausal Women

UNC-GCRC-2107 Prevention 45 to 70 NCI Phase I

Phase I Study of Lycopene as Chemoprevention for Prostate Cancer in Healthy Participants

UIC-2004-0040 Prevention 18 to 45 NCI Phase I

Appendix

73
NCI CAM Annual Report 2005 PDQ Cancer CAM Clinical Trials Active in FY 2005 Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) Phase I Randomized Study of Folate-Depleted Versus Folate-Supplemented Diet for the Prevention of Colorectal Cancer in Patients at High Risk for Colorectal Neoplasia RUH-PHO- 0514-0404 Prevention 40 to 72 NCI Phase I Phase I Study of Resveratrol in Healthy Participants CCUM-2004-0535 Prevention 18 to 80 NCI Phase I Phase I Study of Green Tea Extract (Polyphenon E) 

as Cancer Prevention in Healthy Participants

UARIZ-HSC-0499 Prevention 18 and 

over 

NCI Phase I

Phase I Randomized Chemoprevention Study of Indole-3-carbinol in Healthy Participants

KUMC-HSC-9139 Prevention 18 to 70 NCI Phase I

Phase I Pilot Chemoprevention Study of IH636 Grape Seed Proanthocyanidin Extract in Healthy Postmenopausal Women at High Risk of Developing Breast Cancer

CHNMCIRB-03178 Prevention 40 to 75 NCI Phase I

Phase II Randomized Study of Dietary Soy in Patients With Elevated PSA Levels

CALGB-79806 Prevention 50 and 

over

NCI Phase II

Phase II Randomized Chemoprevention Study of Calcitriol in Patients With High-Grade Prostatic Intraepithelial Neoplasia

CINJ-080404 Prevention 18 and 

over

NCI Phase II

Phase II Randomized Study of Green Tea or Polyphenon E in Preventing Lung Cancer in Former Smokers With Chronic Obstructive Pulmonary Disease

UARIZ-HSC-0353 Prevention; 

Biomarker/Laboratory analysis

40 to 80 NCI Phase II

Phase III Randomized Chemoprevention Study of Selenium in Participants With Previously Resected Stage I Non-Small Cell Lung Cancer

ECOG-5597 Prevention 18 and 

over

NCI Phase III

Phase III Randomized Study of Isoflavones in Reducing Risk Factors in Patients With Stage I or II Prostate Cancer

MCC-0002 Prevention 50 to 80 NCI Phase III

74
Appendix

PDQ Cancer CAM Clinical 

Trials Active in FY 2005 Primary ID

Type ofTrial

AgeRange

Sponsorof Trial Phase(s)

Phase III Randomized Study of Selenium in Patients With Adenomatous Colorectal Polyps

UARIZ-HSC-00142 Prevention 40 to 80 NCI Phase III

Pilot, Randomized Study of Mindfulness Relaxation Versus Relaxing Music Versus Standard Symptom Management Education in Patients With Newly Diagnosed Solid Tumors Undergoing Chemotherapy

MDA-CCC-0106 Supportive care 18 and 

over

NCI No phase specified

Randomized Pilot Study of Low-Residue Diet for the Treatment of Diarrhea in Patients With Uterine, Cervical, or Prostate Cancer Who Are Undergoing Pelvic Radiotherapy

CASE-2Z05 Supportive care 20 to 80 NCI No phase specified

Randomized Pilot Study of Glutamine Supplementation for the Prevention of Paclitaxel-Induced Myalgia and/or Arthralgia in Patients With Cancer

OHSU-ONC99037-L Supportive care 18 and over NCI No phase specified

Study of Acupuncture in Treating Hot Flashes in Patients With Prostate Cancer Undergoing Androgen Deprivation

OHSU-7235 Supportive care Over 18 NCI No phase specified

Randomized Pilot Study of Professional Massage Therapy Versus Professional Simple Presence (No Touch) Massage Therapy Followed By Caregiver Massage Therapy for Symptom Management in Patients With Locally Advanced or Metastatic Cancer

BIDMC-2003P000299 Supportive care 18 and over NCI No phase specified

Pilot Study of Restorative Yoga for Symptom Management and Stress Reduction in Women With Ovarian or Breast Cancer

CCCWFU-02403 Supportive care 18 and 

over

NCI No phase specified

Randomized Study of Coenzyme Q to Relieve TreatmentRelated Fatigue in Women With Breast Cancer CCCWFU-97202 Supportive care Any age NCI No phase specified

75
NCI CAM Annual Report 2005 PDQ Cancer CAM Clinical Trials Active in FY 2005 Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) Randomized Study of Hypnosis, Massage Therapy, and Healing Touch in Patients Undergoing Chemotherapy for Ovarian Epithelial or Primary Peritoneal Cavity Cancer UMN-2000NT790 Supportive care Any age NCI No phase specified Pilot Study of Soy-Based Meal Replacement (Almased®) as a Weight Loss Intervention in Patients With 

Estrogen Receptor/Progesterone Receptor-Negative Stage I-III Breast Cancer in Complete Remission

CCCWFU-98904 Supportive care; 

Educational/Counseling/Training Behavioral study

21 and over

NCI No phase specified

Phase II Randomized Study of Soy Protein in Postmenopausal Women With Breast Disease Taking Tamoxifen and Experiencing Hot Flashes

CALGB-79805 Supportive care Postmenopausal (20 

and over)

NCI Phase II

Phase II Randomized Pilot Study of Massage Therapy in Patients With Cancer Pain

MSKCC-03046A Supportive care 18 and 

over

NCI Phase II

Phase II Randomized Study of Ginger in Patients With Cancer and Chemotherapy-Induced Nausea and Vomiting

CCUM-0201 Supportive care 18 and 

over

NCCAM; NCI Phase II

Phase II/III Randomized Study of Ginger for Chemotherapy-Related Nausea in Patients With Cancer

URCC-U1902 Supportive care 18 and 

over

NCI Phase II; Phase III

Phase III Randomized Study of Zinc Sulfate for the Prevention of Altered Taste in Patients With Head and Neck Cancer Undergoing Radiotherapy

NCCTG-N01C4 Supportive care 18 and 

over

NCI Phase III

Phase III Randomized Study of Acupressure for Chemotherapy-Induced Nausea in Women With Breast Cancer Receiving One of Three Combination Therapy Regimens

MDA-NUR01-396 Supportive care Adult NCI Phase III

76
Appendix

PDQ Cancer CAM Clinical 

Trials Active in FY 2005 Primary ID

Type ofTrial

AgeRange

Sponsorof Trial Phase(s)

Phase III Randomized Study of Juven® Versus a Non-Juven® Supplement in the Treatment of Cachexia in Patients With Unspecified Solid Tumors or Lymphoma With No Leukemic Aspect

RTOG-0122 Supportive care 17 and 

over

NCI Phase III

Phase III Randomized Study of Sertraline (Zoloft®) Versus Hypericum Perforatum (St. John’s Wort) in Cancer Patients With Mild to Moderate Depression

CCCWFU-98101 Supportive care 18 and 

over

NCI Phase III

Phase III Randomized Study of Acupuncture Versus Standard of Care in Treating Pain and Dysfunction in Patients With Head and Neck Cancer Who Have Undergone Neck Dissection

MSKCC-03131A Supportive care Not 

specified

NCI Phase III

Phase III Randomized Study of (Valerian) for Improving Sleep in Patients With Cancer Receiving Adjuvant Therapy

NCCTG-N01C5 Supportive care 18 and 

over

NCI Phase III

Phase III Randomized Study of Creatine in Patients With Cancer-Associated Weight Loss

NCCTG-N02C4 Supportive care 18 and 

over

NCI Phase III

Pilot Study to Evaluate the Influence of Garlic on the Pharmacokinetics of Docetaxel in Patients With Locally Advanced or Metastatic Breast Cancer

NCI-04-C-0084 Treatment 18 and 

over

NCI No phase specified

Randomized Pilot Study of Isoflavones Versus Lycopene Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer

MCC-0105 Treatment; 

Biomarker/Laboratory analysis

45 to 80 NCI No phase specified

Phase I Study of Gemcitabine and Mistletoe in Patients With Advanced Solid Tumors

NCCAM-02-AT-260 Treatment 18 and 

over

NCCAM; NCI; Other

Phase I

Phase I Study of Calcitriol and Gefitinib With or Without Dexamethasone in Patients With Advanced Solid Tumors

RPCI-RPC-0207 Treatment 18 and 

over

NCI; Pharmaceutical Industry Phase I

77
NCI CAM Annual Report 2005 PDQ Cancer CAM Clinical Trials Active in FY 2005 Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) Phase I/II Study of Arsenic Trioxide Plus Ascorbic Acid in Patients With Recurrent or Refractory Multiple Myeloma SCCC-20010 Treatment Over 18 NCI Phase I; Phase II Phase I/II Pilot Study of Scutellaria Barbata (Chinese Herbal Extract) in Women With Metastatic Breast Cancer UCSF-CRO-00758 Treatment 18 and over NCI Phase I; Phase II

Phase I/II Study of Green Tea Extract (Polyphenon E) in Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia

MAYO-MC0419 Treatment 18 and 

over

NCI Phase I; Phase II

Phase II Randomized Study of Soy Protein Isolate (Isoflavones) and Radiotherapy in Patients With Localized Prostate Cancer 

WSU-D-2325 Treatment 18 and 

over

NCI Phase II

Phase II Randomized Pilot Study of Calcitriol and Dexamethasone Before Radical Prostatectomy in Patients With Localized Adenocarcinoma of the Prostate

RPCI-RP-0212 Treatment 18 and 

over

NCI Phase II

Phase II Study of Supplemental Treatment With Mistletoe in Patients With Stage IIIB or IV Non-Small Cell Lung Cancer Receiving Palliative Chemotherapy

TJUH-01F.45 Treatment 18 and 

over

NCI Phase II

Phase II Study of Genistein in Patients With Localized Prostate Cancer and Planned Radical Prostatectomy

NU-00U7 Treatment 18 and 

over

NCI Phase II

Phase II Randomized Prevention Study of Fatand/or Flaxseed-Modified Diets in Patients With Newly Diagnosed Prostate Cancer

DUMC-1385-02-7R3ER

Treatment 18 and 

over

NCI Phase II

Phase II Study of Pomegranate Juice in Patients With Indication of Recurrent Adenocarcinoma of the Prostate

UCLA-0210049 Treatment 18 and 

over

NCI Phase II

Phase II Randomized Study of Fruit and Vegetable Extracts in Patients With Stage I-IVB Head and Neck Cancer

CCCWFU-0112 Treatment 18 and 

over

NCI Phase II

78
Appendix

PDQ Cancer CAM Clinical 

Trials Active in FY 2005 Primary ID

Type ofTrial

AgeRange

Sponsorof Trial Phase(s)

Phase II Study of Lycopene in Patients With Asymptomatic Androgen-Independent Metastatic Prostate Cancer Who Have an Elevated Prostate-Specific Antigen Level

NCCTG-N0351 Treatment 18 and 

over

NCI Phase II

Phase II Study of High-Dose Pulse Calcitriol, Mitoxantrone, and Prednisone in Patients With Androgen-Independent Metastatic Prostate Cancer

OHSU-8451 Treatment 18 to 100 NCI Phase II

Phase II Study of Genistein, Gemcitabine Hydrochloride, and Erlotinib Hydrochloride in Patients With Locally Advanced or Metastatic Pancreatic Cancer

WSU-2005-006 Treatment 21 and 

over

NCI Phase II

Phase II Randomized Study of Neoadjuvant Genistein in Patients Undergoing Surgical Resection for Bladder Cancer

WCCC-CO-04307 Treatment 18 and 

over

NCI Phase II

Phase II Randomized Study of Adjuvant Combined With a Low-Fat, Arachidonic Acid-Free Vegan Diet Versus a Standard Diet Alone in Patients With Newly Diagnosed Glioblastoma Multiforme

CASE-CCF-7348 Treatment 18 and 

over 

NCI Phase II

Phase II Randomized Study of Neoadjuvant Dietary Supplementation With Soy in Patients Undergoing Radical Prostatectomy for Localized Prostate Cancer

CCCWFU-98203 Treatment; 

Biomarker/Laboratory analysis

Over 18 NCI Phase II

Phase II Randomized Study of Soy Isoflavones Before Radical Prostatectomy in Patients With Stage I or II Adenocarcinoma of the Prostate

WSU-C-2418 Treatment; 

Prevention

18 and over

NCI Phase II

Phase III Randomized Study of Induction PlatinumBased Chemotherapy and Radiotherapy With or Without AE-941 (Neovastat) in Patients With Unresectable Stage IIIA or IIIB Non-Small Cell Lung Cancer

MDA-ID-99303 Treatment 18 and 

over

NCCAM; NCI Phase III

79
NCI CAM Annual Report 2005

Office of 

Management

Office Of 

International Affairs

NCI-Frederick

Office of Budget 

And Financial 

Management

Office of Cancer 

Complementary 

And Alternative 

Medicine

Center for 

Bioinformatics

Office of Workforce 

Development

Office of 

Communications

Office of Policy, 

Analysis & 

Response

Ethics Office

Office of Education 

And Special 

Initiatives

Center for 

Advanced 

Technologies 

and Strategic 

Partnerships

Office of Science 

Planning and 

Assessment

Center to Reduce 

Cancer Health 

Disparities

Office of Centers, 

Training and 

Resources

Coordinating 

Center for 

Clinical Trials

Office of the Director Special Assistant 

for Program 

Coordination

Organizational 

Chart

80
Illustration Credits

p. 31: Milk Thistle 

© 1995-2005 Missouri Botanical Garden

http://www.illustratedgarden.org

p. 37: Black Raspberry

courtesy USDA Pomological Watercolor Collection, 

Special Collections, National Agricultural Library

p. 39: Prunella Vulgaris

courtesy Herbarium of The New York Botanical Garden

http://sciweb.nybg.org/science2/Virtual Herbarium.asp

p. 63: Lemon

© 1995-2005 Missouri Botanical Garden

http://www.illustratedgarden.org
NIH Publication No. 06-6011

 Printed January 2007