NCI Office of Cancer Complementary and Alternative Medicine CI Office of Cancer Complementary and Alternative Medicine 

National Cancer Institute
 

NCI’s Annual Report on 

Complementary and 

Alternative Medicine 

Fiscal Year 2006 

U.S. DEPARTMENT 

OF HEALTH AND 

HUMAN SERVICES 

National Institutes 

of Health 

DIRECTOR’S MESSAGE

Director’s Message
 

The research the National Cancer Institute (NCI) 

supports, at universities across the country and in 

our NCI laboratories, is focused on the ultimate 

goal of helping cancer patients. That mission – 

achieved through intricate research and rigorous 

science – most certainly extends, as well, to NCI’s 

study of complementary and alternative medicine, 

also known as CAM. 

This report offers a window into NCI’s 

accomplishments in advancing evidence-based 

CAM interventions and therapies, along with 

some perspective on our efforts to more fully 

understand their efficacy, because of the genetic 

and biological differences between patients. It is 

important that physicians caring for patients with 

cancer know which CAM therapies are compatible 

with standard chemotherapy methods and with 

medicines we use to combat the symptoms 

associated with treatment. 

Because cancer is a disease of such complexity, 

CAM must be an integrated part of the larger 

research enterprise, touching on many other 

areas, including studies of basic tumor biology, 

drug design, nutrition, and behavioral medicine. 

Consequently, NCI’s portfolio of CAM research 

is distributed throughout many of the Institute’s 

programs. 

The Office of Cancer Complementary and 

Alternative Medicine supports this research 

through its efforts to attract experienced investigators to work in this important area of science. 

I hope you find this report helpful. I also 

hope that it will generate increased dialogue – 

especially between patients and their healthcare 

professionals – about the appropriate uses of 

CAM, in conjunction with conventional medicine. 

Cancer patients deserve credible, unbiased information about any intervention or treatment 

regimen that they are considering. It is our duty 

to conduct the science that makes their wise 

decisions possible. 

John E. Niederhuber, M.D. 

Director 

National Cancer Institute 

NCI CAM Annual Report 2006 1 

Table of Contents
 

1 Director’s Message 

5 Introduction 

7 Office of Cancer Complementary and Alternative Medicine 

13 NCI CAM Communications Programs 

17 Training and Conferences 

21 NCI Research in Complementary and Alternative Medicine 

25 MAJOR ACCOMPLISHMENTS IN 2006 

26 Studies Suggest Exercise Improves Colorectal Cancer Outcomes 

28 Low-Fat Diet May Have Small Impact on Breast Cancer in Women 

29 ADDRESSING NCI’S STRATEGIC AREAS WITH EXTRAMURAL RESEARCH 

30 Understanding the Causes and Mechanisms of Cancer 

31 Antioxidants and Chemotherapy: Help or Hindrance? 

32 Calcium and Vitamin D May Help Prevent Colorectal Cancer 

34 Accelerating Progress in Cancer Prevention 

35 Lycopene Studied for the Prevention of Lung Cancer 

36 Concentrated Vitamin D May Slow Prostate Cancer 

37 Improving Cancer Prevention Strategies Using the Biological Clock 

38 Developing Effective and Efficient Treatments 

39 Ginseng Studied as Possible Breast Cancer Treatment 

40 Noni Juice Studied for Prevention of Breast Cancer 

41 Studying the Effects of Vitamin E and Soy During Radiation for Prostate Cancer 

42 Disrupting a Tumor’s Biological Clock to Improve Treatment Responses 

44 Improving the Quality of Cancer Care 

45 Soy Protein Studied for Men at High Risk of Prostate Cancer Recurrence 

46 Flaxseed and Curcumin for the Prevention of Radiation-Induced Lung Injury 

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

49 Tai Chi Chih Effects on Insomnia Studied in Breast Cancer Patients 

50 Study Will Test the Effect of Tibetan Yoga on Women with Breast Cancer 

51 Hypnotherapy Eases Hot Flashes in Breast Cancer Survivors 

52 NCI SCIENTISTS SPEARHEAD PIONEERING RESEARCH ON CAM 

53 NCI Scientists Are Using Mice to Study Selenium and Resveratrol’s Role in Cancer Prevention 

54 NCI Researcher Investigates How Selenium Protects Against Cancer 

55 NIH-AARP Diet and Health Study Examines Links Between Nutrition, Weight, and Cancer 

56 Exploring the Role of Cooked Red Meat in Cancer Risk 

57 Scientific Publications 

60 Appendix 

NCI CAM Annual Report 2006 3 
FIGURE 1. Major Categories of CAM Therapies 

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. There are two types: 


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 

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: tai 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: Mind-body medicine uses 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 nonnutrients, 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, immuno-augmentation 

therapy, laetrile, hydrazine sulfate, melatonin. 

Sub-category: Complex Natural Products 

Definition: An assortment of plant samples 

(botanicals), extracts of crude natural substances, 

and un-fractionated 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 
INTRODUCTION

Introduction 


Each year, Congress requests a report of NCI’s 

annual expenditures in complementary and alternative medicine* (CAM) research. To give more 

meaning to the numbers provided to Congress, a 

more detailed account of the Institute’s investment in CAM was produced for the first time last 

year. That report, NCI’s Annual Report on 

Complementary and Alternative Medicine: Fiscal Year 

2005, was created as a way for NCI to communicate its progress in this area of medical research, 

not only to Congress but also to other interested 

stakeholders including cancer researchers, CAM 

practitioners, health care providers, advocacy 

organizations, and the general public. 

This year, the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM) 

is proud to present the second such report, NCI’s 

Annual Report on Complementary and Alternative 

Medicine: Fiscal Year 2006. Similar to the FY 2005 

report, this publication provides an overview of 

the NCI-supported work in this field along with 

details on certain specific projects in the areas of 

cancer CAM relating to communication, training 

and conferences, and research. 

This report highlights projects, grants, and 

cooperative agreements supported by each of the 

Institute’s extramural grant funding divisions – 

Division of Cancer Biology (DCB), Division of 

Cancer Control and Population Sciences (DCCPS), 

Division of Cancer Prevention (DCP), and Division 

of Cancer Treatment and Diagnosis (DCTD) 

along with projects from NCI’s intramural laboratories – Center for Cancer Research (CCR) and 

Division of Cancer Epidemiology and Genetics 

(DCEG). These projects represent a variety of 

CAM categories, cancer types, research types, and 

grant mechanisms. Also included in the report is a 

breakdown of NCI’s CAM research portfolio. In 

FY 2006, NCI’s research expenditures for CAM 

are an estimated $123,076,167 for the funding of 

461 CAM research projects. 

As this report on cancer CAM indicates, we at 

the NCI are 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 evidence-based CAM techniques, 

systems, and products can have an important role 

in helping us reach that worthwhile goal. 

*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, acupuncture, massage therapy, magnet 

therapy, spiritual healing, and meditation. (See Figure 1, on page 4 for the major categories of CAM therapies.) 

NCI CAM Annual Report 2006 5 

Office of Cancer Complementary 


and Alternative Medicine
 

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

is a coordinating office for NCI involved in: identifying gaps in the science 

and creating corresponding funding opportunities in relation to CAM; 

partnering with NCI program staff and other governmental and 

nongovernmental organizations to increase the testing of CAM approaches 

with regards to cancer prevention, diagnosis, treatment, symptom 

management, and rehabilitation; developing communication products for 

various audiences concerning the investigation of these approaches; and 

helping to build bridges between CAM practitioners and the cancer 

research community. 
NCI OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE 

OCCAM Programs Highlights of the 

RDSP Research Portfolio 

Research Development and 

Support Program In FY 2006, OCCAM began funding grants and 

cooperative agreements that will substantially 

As previously noted, NCI sponsors more than expand NCI’s support of the exploration of 

460 cancer CAM research projects, each of which traditional non-Western medical systems for antiare managed within the various Divisions and cancer therapies. 

Centers of the Institute. The Research Development and Support Program (RDSP) staff manages International Center for the Evaluation of East 

a portion of this portfolio and works with other Asian Botanicals for Cancer – Investigators at 

program staff throughout the NCI, assists Harvard University, in collaboration with the 

investigators in identifying funding opportunities, Chinese University of Hong Kong and Hong 

and provides guidance in the pre- and post-review Kong Baptist University, initiated a project to 

periods of grant application. The staff also coor- establish the first library of authenticated medicidinates programs and initiatives designed to nal plants, extract each plant according to stanstimulate research in cancer CAM as well as dardized protocols, fractionate the extracts using 

activities to develop the foundation of the science reproducible methods, and then test individual 

in cancer CAM research. extracts as well as combinations of extracts (and 

In FY 2006, RDSP’s program announcement fractions) systematically for their anti-cancer 

series PAR-02-040 and PA-04-053 was one of the biological properties. Ultimately, the extracts 

most productive mechanisms for attracting new and/or fractions from these candidate plants 

CAM grants to NCI. A total of 46 of the 167 which demonstrate anti-cancer properties in 

solicited CAM grants active in FY 2006 came preclinical studies will next be tested in relevant 

to NCI through these two announcements. (See animal models. Results of animal studies will then 

Figure 2) The RDSP staff also worked with staff be used to plan appropriate human clinical trials. 

of other NCI programs to fund new grants and Through a combination of Traditional 

supplements to existing grants. Chinese Medicine (TCM) expertise, the leveraging 

of biotechnology at Harvard, and substantial NCI 

involvement, this project will directly address 

many of the shortcomings of previous botanical 

research in this area. It will establish a future 

FIGURE 2. Cancer CAM-related Grants Awarded in FY 06 by Program Announcement (PA) 

and Request for Applications (RFA) 

AT03-002 2 CA03-004 3 CA05-013 2 PA03-041 0 PA05-027 1 PAR01-110 1 PAR04-147 0 

CA01-020 1 CA03-006 1 CA99-003 1 PA03-169 0 PA05-125 1 PAR02-037 1 PAR04-155 1 

CA02-003 2 CA03-007 0 ES02-009 1 PA03-053 1 PA05-141 1 PAR02-040 28 PAR04-159 0 

CA02-007 2 CA03-016 0 ES05-007 1 PA04-034 1 PA06-041 2 PAR02-176 1 PAR05-156 1 

CA02-008 1 CA03-018 1 OD03-008 1 PA04-053 17 PA06-120 1 PAR03-009 0 PAR06-073 1 

CA02-009 2 CA04-001 1 PA00-080 0 PA04-068 0 PA96-008 1 PAR03-010 3 PAR99-167 0 

CA03-001 3 CA04-002 1 PA01-015 1 PA04-099 4 PA99-163 0 PAR03-153 5 PAS02-009 0 

CA03-003 8 CA04-004 5 PA02-001 0 PA04-108 2 PA99-081 1 PAR03-176 0 Unsolicited 141 

CA03-004 3 CA04-008 1 PA02-124 2 PA04-146 1 PAR00-025 1 PAR04-011 0 TOTAL 195 

8 NCI CAM Annual Report 2006 
A SCREENING OF THE NEW MEDICINE 

On April 24, 2006, RDSP organized and hosted a screening of a portion of The New Medicine, a 

two-part documentary on mind-body medicine research produced by Middlemarch Films and 

Twin Cities Public Television. The screening was held for staff members from the National Center 

for Complementary and Alternative Medicine (NCCAM), the National Institute of Mental Health 

(NIMH), the Office of Behavioral and Social Sciences Research, and NCI. Dr. Margaret Chesney 

of NCCAM and Dr. Esther Sternberg of NIMH, both featured in the documentary, answered 

questions concerning the featured research studies and concepts. 
NCI OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE 

model for systematically identifying medicinal 

plant extracts, compounds, and combinations of 

extracts with clinically significant anti-cancer 

effects. (Grant number: 1U19CA128534-01) 

Cancer Prevention by West African Medicinal 

Plants – West Africa is rich in indigenous medicinal 

practices including knowledge of and use of 

botanicals with extensive anti-inflammatory effects. 

The overall goal of this project at the Palmetto 

Health System of South Carolina is to discover 

novel, anti-inflammatory compounds from medicinal plants native to West Africa. The broad, longterm objective is to establish a role for this 

unexploited source of natural products for future 

chemoprevention applications for colon and other 

cancers. (Grant number:1R21CA107138-01A2) 

Communications and Outreach Program 

OCCAM’s Communications and Outreach Program 

(COP) develops and disseminates information 

about NCI program initiatives and funding 

opportunities, workshops and other events, and 

educational materials through OCCAM’s Web site 

(www.cancer.gov/cam) and publications. 

Cancer CAM Research Funding Directory 

This program also assesses the opinions, 

interests, and informational needs of cancer 

researchers, CAM practitioners, and cancer 

patients regarding CAM research through surveys, 

public comment sessions, and focus groups. 

Results from these explorations are used to guide 

outreach efforts to these communities. 

•	 COP developed the following products in 


FY 2006:
 

•	 NCI Best Case Series Brochure 

•	 OCCAM Brochure 

•	 NCI CAM News – Winter 2006 and Summer 

2006 issues 

•	 Strategies for Success: How to Write a Grant in 


Cancer CAM
 

Practice Assessment Program 

OCCAM’s Practice Assessment Program (PAP) 

reviews retrospective and prospective data on 

cancer patients treated with alternative therapies. 

PAP manages the NCI Best Case Series (BCS) 

Program, which provides an opportunity for 

CAM practitioners to submit medical data regarding 

cancer CAM treatments used in their settings. 

Practitioners are asked to submit patient records 

Securing federal funding for research is often challenging. To assist researchers in finding other funding opportunities 

for their cancer CAM research projects, OCCAM developed a non-NIH funding directory. This directory is updated 

periodically and consists of foundations, advocacy groups, non-federal government organizations, and private sector 

organizations that have expressed an interest in funding cancer CAM research. Contact information and specific 

areas of CAM interests are provided for each organization. 

The directory can be viewed and downloaded from http://www.cancer.gov/cam/attachments/occam-researchfunding-directory.pdf. 

OCCAM Announcements 

To support the program goal of disseminating information, OCCAM has created the e-mail distribution list OCCAM 

Announcements. OCCAM Announcements provides individuals who have an interest in cancer CAM with timely 

notifications about new funding opportunities, upcoming workshops and lectures, publications, and other resources. 

To subscribe online for OCCAM Announcements, go to http://www.cancer.gov/cam/news/occamannouncements.html. 

10 NCI CAM Annual Report 2006 
NCI OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE 

for evaluation by experts in clinical assessment 

and cancer treatment research. Results of the NCI 

BCS Program are used to inform decisions 

regarding NCI-initiated research and to share 

well-documented best cases with interested 

members of the scientific community in order to 

stimulate research. 

In FY 2006, OCCAM released two broad 

agency announcements related to the NCI BCS 

Program. The first announcement (N01-CO57034-48) was designed to support a contract 

proposal for the preparation of a best case series 

submission and prospective research on a CAM 

therapy if the submission review shows that the 

criteria have been fully met. A contract awarded as 

a result of the second announcement (N01-CO57035-48) would provide support for prospective 

research (preclinical, clinical trial, or both) on 

specific alternative medicine approaches that have 

already completed the NCI BCS Program process. 

More OCCAM Highlights 

Traditional Chinese Medicine and Cancer 

Research: Fostering Collaborations; 

Advancing the Science 

OCCAM hosted an ambitious conference titled 

“Traditional Chinese Medicine and Cancer 

Research: Fostering Collaborations; Advancing 

the Science,” held in April 2006 at the National 

Institutes of Health (NIH) campus in Bethesda, 

Maryland. This endeavor took six months of 

planning and was prompted by multiple meetings 

with the China Academy of Chinese Medical 

Sciences (CACMS), a national center for TCM 

research, teaching, and health care in China. 

Over 150 scientists and physicians attended 

the conference, including more than 40 who 

traveled from China to participate. While the conference included posters and presentations like a 

standard biomedical gathering, its main purpose 

was to serve as an incubator for establishing new 

collaborative relationships between Chinese and 

Western scientists, particularly NCI intramural 

researchers, interested in exploring TCM for 

cancer prevention, treatment, and palliation. 

OCCAM’s Participation at Major 

Professional Conferences 

OCCAM staff members are active in both 

domestic and international professional conferences through presentations and engaging in dialog 

with cancer CAM researchers, practitioners, and 

patient advocacy groups. (See also Training and 

Conferences on pg. 17). During FY 2006, this 

encompassed several important meetings: 

•	 In November 2005, Dr. Oluwadamilola 

Olaku presented “Survey of Researchers and 

Practitioners Regarding Complementary and 

Alternative Medicine” at the Society for 

Integrative Oncology in San Diego, California. 

•	 On February 23, 2006, Dr. Jeffrey D. White 

presented “Clinical Research on CAM in 

Cancer: NCI’s Perspective” at the meeting 

on Controversies about Complementary and 

Alternative Medicine (CAM) in Oncology in 

Brussels, Belgium. 

•	 On April 7, 2006, Dr. Wendy B. Smith 

presented “Research and Funding 

Opportunities in Pain Medicine at NIH” 

at the Integrative Pain Medicine Course at 

Columbia University. 

•	 On April 30, 2006, Shea Buckman, M.A. 

presented “Cancer CAM Information 

Resources” at the National Breast Cancer 

Coalition Fund Annual Meeting in 

Washington, D.C. 

•	 In May 2006, CDR (USPHS) Colleen Lee, 

CRNP, AOCN® presented “NCI Best 

Case Series Program: Goals, Criteria, and 

Outcome Measures” at the North American 

Research Conference on Complementary 

Medicine in Edmonton, Canada. 

NCI CAM Annual Report 2006 11 
NCI OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE 

OCCAM’s Exhibit Program 

In addition, OCCAM expanded its outreach 

efforts through exhibiting or sending publications 

to numerous professional meetings: 

•	 American Holistic Medical Association 

•	 American Association of Naturopathic 

Physicians 

•	 Society for Integrative Oncology 

•	 American College for the Advancement of
 

Medicine
 

•	 American Association for Cancer Research 

•	 Oncology Nursing Society 

•	 American Society for Clinical Oncology 

•	 American Association of Family Physicians 

OCCAM Staff List: FY 2006 

Working with Advocates 

In FY 2006, OCCAM staff had several opportunities 

to work with representatives of the cancer patient 

advocacy community including the following: 

•	 Presenting at two sessions of the National 

Breast Cancer Coalition Fund Annual Meeting 

•	 Exhibiting on June 19, 2006 at the Director’s 

Consumer Liaison Group Poster Picnic, an 

activity of the NCI consumer summit meeting 

Listening and Learning Together: Building a Bridge 

of Trust 

•	 Working with five advocates within the NCI’s 

Consumer Advocates in Research and Related 

Activities program on the review of a draft 

of NCI’s Annual Report on Complementary and 

Alternative Medicine: Fiscal Year 2005 

•	 Hosting a national question and answer forum 

on the NCI’s Listens and Learns Web site, a 

pilot program designed to improve communication and collaboration between NCI, the 

cancer advocacy community, and the public 

Jeffrey D. White, M.D. Director, OCCAM 

Wendy B. Smith, Ph.D., B.C.I.A.C. Director, Research Development and Support Program 

CDR (PHS) Colleen Lee, M.S., AOCN® Coordinator, Practice Assessment Program 

Shea Buckman, M.A. Coordinator, Communications and Outreach Program 

Tai N. Baker, M.P.H. Communications Analyst 

Christina Armstrong Administrative Program Specialist 

Ashanti Certain Office Assistant 

Dan Xi, Ph.D. Biologist 

Oluwadamilola Olaku, M.D., MRCOG Scientific Program Analyst 

Phil Tonkins, Dr.P.H. Scientific Program Analyst 

Libin Jia, M.D. Scientific Program Director (on detail) 

Karen Alladin, M.S. CRTA Fellow 

Elisabeth Beaver, M.S. CRTA Fellow 

12 NCI CAM Annual Report 2006 
NCI CAM
 

Communications Programs
 

NCI directs communications programs that are committed to providing 

current and credible information resources about CAM to its stakeholders. 
NCI CAM COMMUNICATIONS PROGRAMS 

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 cancer 

treatment, prevention, and screening summaries – 

called Physician Data Query (PDQ®) summaries – 

including certain CAM therapies as well as shorter question and answer documents (Fact Sheets). 

During FY 2006, NCI released the patient version 

PDQ summary Aromatherapy (http://www.cancer.gov/cancertopics/pdq/cam/aromatherapy/p 

atient), bringing the total number of CAM-related 

summaries to 17. 

Online access is also provided to NCI’s PDQ 

Cancer Clinical Trials Registry. This registry 

includes approximately 4,500 abstracts of protocols 

that are open and approved to accept patients, 

including 74 clinical studies on CAM approaches 

for cancer (See appendix). 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. 

In FY 2006, a newly designed CAM clinical 

trials search table was added to the OCCAM Web 

site. Similar to the search function on the NCI 

Web site, this new search table provides direct 

access to the entire list of cancer CAM clinical trials, 

including those clinical trials which have already 

closed. The new clinical trials search table also 

allows users to view active CAM clinical trials by 

either cancer type or an associated symptom. 

At the present time, there are approximately 

15 cancer types listed as active CAM clinical trials. 

Examples include: 

• Bladder cancer 

• Head and neck cancer 

• Lung cancer 

• Prostate cancer 

There are active CAM clinical trials for six 

common symptoms: 

• Anorexia 

• Hot flashes 

• Fatigue 

• Nausea 

• Pain 

• Oral complications 

For the complete list of CAM clinical trials by 

cancer type and to access the CAM clinical trials 

table, go to http://www.cancer.gov/cam/clinical 

trials_list.html. 

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. 

Award for Cancer CAM Booklet 

The informative booklet Thinking About Complementary and Alternative Medicine won the bronze
 

National Health Information Award in 2006. Written by OCCAM, in conjunction with NCI’s Office of
 

Education and Special Initiatives and NIH’s NCCAM, this publication has since been translated into
 

both French and Italian. 


Download the booklet online at http://www.cancer.gov/cancertopics/thinking-about-CAM or 

order 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. 

14 NCI CAM Annual Report 2006 
NCI CAM COMMUNICATIONS PROGRAMS 

Producing Publications 

In addition to the OCCAM Web site, various 

offices within NCI provide educational materials 

on CAM in print formats to health professionals, 

people affected with cancer, and consumers. 

NCI’s First Annual Report on CAM 

OCCAM published NCI’s Annual Report on 

Complementary and Alternative Medicine: Fiscal Year 

2005, which was the first report of its kind documenting NCI’s participation in and support of 

a wide range of CAM activities. The report 

highlights the contributions of communications 

programs, training and conferences, and cancer 

CAM research in addressing the NCI strategic 

areas to support the elimination of suffering and 

death due to cancer. Copies of the report can 

be viewed and downloaded from http://www. 

cancer.gov/cam/attachments/CAMAnnualRepo 

rtFY2005.pdf. 

Newsletter on NCI’s CAM Activities 

OCCAM also launched a biannual newsletter NCI 

CAM News to provide the latest information on 

NCI-sponsored research, funding opportunities, 

meetings and workshops, as well as educational 

information on cancer and CAM. The inaugural 

issue introduced OCCAM’s programs and highlighted its activities. Subsequent issues include 

features on cancer CAM projects representing the 

full range of NCI’s activities as well as OCCAM 

program updates. The following FY 2006 issues of 

NCI CAM News are available online: 

•	 Winter 2006 

http://www.cancer.gov/cam/newsletter/ 

2006-winter/home.html 

•	 Summer 2006 

http://www.cancer.gov/cam/newsletter/ 

2006-summer/home.html 

CAM in the NCI Cancer Bulletin 

The NCI Cancer Bulletin is a biweekly online newsletter designed to provide useful, timely information about cancer research to the cancer research 

community. OCCAM was featured in three issues 

of the NCI Cancer Bulletin during FY 2006: 

•	 CAM Scientist Tests Lung Cancer Herb; 

February 14, 2006 (Volume 3, Number 7) 

•	 Conference Promotes Collaborations in Traditional 

Chinese Medicine Research; April 18, 2006 

(Volume 3, Number 16) 

•	 NCI CAM Newsletter Debuts; April 25, 2006 

(Volume 3, Number 17) 

In addition, there were also several cancer CAM 

studies featured in the NCI Cancer Bulletin during 

FY 2006: 

•	 Carnitine Supplementation for Cancer-Related 

Fatigue; January 3, 2006 (Volume 3, Number 1) 

•	 American Ginseng for Cancer-Related Fatigue; 

January 24, 2006 (Volume 3, Number 4) 

•	 Omega-6 Fatty Acid Activates Genes Linked to 

Prostate Cancer Development; February 14, 2006 

(Volume 3, Number 7) 

•	 Saw Palmetto Fails to Improve Benign Prostate 

Hyperplasia; February 14, 2006 (Volume 3, 

Number 7) 

The NCI fact sheet “Complementary 

and Alternative Medicine in Cancer 

Treatment: Questions and Answers” 

was viewed 31,800 times in FY 2006. 

To view this publication, please visit 

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

factsheet/therapy/cam. 

NCI CAM Annual Report 2006 15 
NCI CAM COMMUNICATIONS PROGRAMS 

Responding to CAM Cancer Inquiries 

The Cancer Information Service (CIS) serves as 

NCI’s link to the public by interpreting and 

explaining research findings in a clear and understandable manner and providing personalized 

responses to specific questions about cancer. 

Highly trained cancer information specialists are 

available to answer questions via phone, live online 

chat, mail, and e-mail about cancer treatment and 

clinical trials, including CAM therapies. During FY 

2006, CIS responded to more than 1,600 inquiries 

regarding CAM approaches for cancer. 

Access the CIS by calling 1-800-4-CANCER 

(1-800-422-6237), or by using the LiveHelp 

instant-messaging service at https://cissecure. 

nci.nih.gov/livehelp/welcome.asp. 

CAM 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. 

OCCAM collects this information via surveys and 

focus groups. Results from these explorations will 

be used to develop programs that are most helpful 

for these audiences. 

In FY 2006, OCCAM conducted two focus 

groups at the Society for Integrative Oncology 

2nd International Conference in San Diego, 

California. A total of 23 cancer CAM researchers 

and CAM practitioners participated in the focus 

group discussions. The main objectives were to 

explore the experiences of cancer researchers and 

CAM practitioners in conducting research on 

CAM and identify existing obstacles and opportunities. An additional objective was to obtain information about participants’ perceptions of CAM 

practices and the degree of involvement the 

participants have in cancer CAM research relative 

to the areas of treatment, symptom management, 

and/or prevention. 

16 NCI CAM Annual Report 2006 
Training and Conferences
 

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

research including grant writing workshops and scientific conference 

sponsorships. 
TRAINING AND CONFERENCES 

Training Opportunities at OCCAM 

During FY 2006, OCCAM hosted two Cancer 

Research Training Award (CRTA) fellows within 

the office, Karen Alladin, M.S. and Elisabeth 

Beaver, M.S. Mentored by Dr. Jeffrey D. White, 

the goals for the two pre-doctoral fellows were to 

learn about the NIH grant process, explore 

approaches to building cancer CAM research, and 

help provide support to the OCCAM programs. 

Each fellow worked on a literature review project 

which will be submitted for publication. 

In addition, OCCAM also hosted a Health 

Communications Intern, Tai N. Baker, MPH, who 

helped plan and organize a scientific conference, 

develop publications and other promotional 

materials, and managed OCCAM’s Web site. Ms. 

Baker also participated in professional meetings 

and NIH-sponsored training seminars. 

Awards for DCEG Fellows 

The NIH Fellows Award for Research Excellence 

program recognizes outstanding scientific research 

by intramural postdoctoral fellows. In FY 2006, 

three DCEG fellows received awards for their 

CAM-related projects: 

•	 Larissa Korde, M.D., M.P.H.: Early life soy intake 

and breast cancer risk in Asian American Women 

•	 Kenneth F. Adams, Ph.D.: Association between 

body mass and colon cancer in the NIH-AARP 

Diet and Health Study 

•	 Amanda J. Cross, Ph.D.: Red meat intake and 

increase risk of colorectal cancer in the NIHAARP Diet and Health Study 

Establishing a CAM Monthly 

Lecture Series at NCI 

In January 2006, OCCAM introduced a new educational outreach program, the OCCAM Monthly 

Lecture Series. This program was developed to 

inform the NCI community about recent and 

ongoing research projects in cancer CAM. These 

hour-long lectures feature a fifty-minute presentation on a cancer CAM topic and allow 10 minutes 

for questions. The lectures are open to the public 

and also are archived on the OCCAM Web site. 

During FY 2006, the series included lectures on: 

•	 Ascorbic acid and tight control: unexpected 

consequences for cancer treatment 

•	 Lung cancer chemoprevention using 

herbal agents 

•	 Traditional medicines and the prevention 


of colon cancer 


•	 Targeting inflammation by dietary agents 

for prevention and treatment of cancer 

•	 Zyflamed-mediated inhibition of proliferation 

of human prostate cancer: preclinical 

pharmacology and clinical trial results 

18 NCI CAM Annual Report 2006 
TRAINING AND CONFERENCES 

Supporting Scientific Conferences 

Society of Integrative Oncology 

A good example of NCI’s support of scientific 

cancer CAM conferences is the Society of 

Integrative Oncology’s (SIO) 2nd International 

Conference in San Diego, California, November 

10-12, 2005. OCCAM staff participated in 

program development and provided conference 

grant support* to SIO for its conference. In addition, Dr. Oluwadamilola Olaku, an OCCAM 

Scientific Program Analyst, gave a presentation 

titled “Survey of Researchers and Practitioners 

Regarding Complementary and Alternative 

Medicine.” The abstracts from the meeting are 

available in the December 2006 issue of the 

Journal of the Society of Integrative Oncology. 

Grant number: *1R13CA126426-1 

North American Research Conference on 

Complementary and Integrative Medicine 

On May 24-27, 2006, the North American 

Research Conference on Complementary and 

Integrative Medicine, supported in part by a grant 

from NCI and NCCAM, was held in Edmonton, 

Canada. This conference presented basic and 

clinical research on complementary and integrative 

therapeutic approaches and promoted educational 

collaboration across multiple medical disciplines. 

During this meeting, researchers and health care 

providers examined and addressed the validity of a 

variety of complementary and integrative medicine 

approaches including massage, herbal therapies, 

acupuncture, dietary supplements, yoga, hypnosis, 

mind-body, and lifestyle approaches to patient 

care. The Consortium of Academic Health 

Centers for Integrative Medicine, which consists 

of 32 leading schools of medicine in the United 

States and Canada, sponsored the conference. 

OCCAM’s PAP Coordinator CDR (USPHS) 

Colleen Lee, M.S., CRNP, AOCN®, presented “NCI 

Best Case Series Program: Goals, Criteria, and 

Outcome Measures.” 

Conference Presentations by NCI 

NCI Deputy Director Mark Clanton, M.D., and 

Mary Anne Bright, director of NCI’s Cancer 

Information Service (CIS), spoke at the NonConventional Treatments for Cancer Patients: How to 

Provide Reliable Information meeting in Rome, Italy 

on December 16, 2005. The conference was 

sponsored by the Associazione Italiana Malati di 

Cancro (AIMaC), the Italian version of NCI’s CIS. 

OCCAM Director Jeffrey White, M.D., gave a 

presentation on NCI’s perspective on clinical 

research on CAM at a European conference on 

“Controversies about CAM in Cancer” which 

took place February 2006 in Brussels, Belgium. 

Finally, the Oncology Nursing Society (ONS) 

sponsored its first all-day session on the Cancer 

CAM Primer for Oncology Nurses at ONS’s 31st 

Annual Congress in Boston, Massachusetts in 

May 2006. OCCAM PAP Coordinator Commander 

(CDR) Colleen O. Lee was a presenter and helped 

develop the session. The content was tailored 

to nurses whose practices span the range from 

community settings and hospitals, to researchbased facilities. Therefore, areas of expertise 

encompassed the care of cancer patients within 

acute, chronic, and supportive care settings. 

As a result of the success of the ONS’ 

Cancer CAM Primer, a cancer CAM supplement 

will be submitted to the Society’s two peerreviewed journals The Oncology Nursing Forum and 

The Clinical Journal of Oncology Nursing. In addition, 

a pocket guide will be published highlighting 

the evidence-based conventional and CAM interventions for the symptoms that were discussed in 

the Primer session at the ONS conference. 

NCI CAM Annual Report 2006 19 

NCI Research in Complementary 


and Alternative Medicine
 

One of OCCAM’s duties as NCI’s coordinating office on CAM is to conduct 

an analysis of the Institute’s expenditures on CAM research for each fiscal 

year. The analysis of both the intramural and extramural CAM research 

portfolios serves to: respond to Congressional inquiries on NCI’s investment 

in this area; determine trends of funding in particular topics; refine NCI’s 

definition of CAM; identify research gaps in the field of cancer CAM; and 

encourage dialog about the potential direction of future cancer CAM 

research. This yearly analysis is an exercise that reveals an estimated total 

amount of funding that goes to cancer CAM research projects and provides 

breakdowns according to the type of research (prevention, treatment, side 

effects/symptom management, and epidemiology), CAM category, and 

cancer type. 

$0

NCI CAM Research Portfolio 

Analysis: FY 2006 

NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

Total Estimated Cancer CAM Research 

Expenditure 

In FY 2006, NCI invested $123,076,167 for 461 

intramural and extramural research projects of 

which some portion addresses CAM. For the 

purpose of the FY 2006 analysis, the following 

types of funding are included: intramural projects 

and extramural grants, cooperative agreements, 

contracts, and supplements. Training grant awards 

(Ts, Fs, Ks, and R25s) were excluded. (See Figure 3.) 

Breakdown by Research Type 

The accompanying pie-chart (Figure 4) shows the 

distribution of the projects by prevention, treatment, symptom/side effects management, epidemiology, and conferences. In FY 2006, 67.85% of 

cancer CAM-related research project funds went to 

various cancer prevention efforts, while treatment, 

symptom/side effects management, epidemiology, 

and conferences received 21.13%, 7.37%, 3.37%, 

and .28% respectively. 

FIGURE 3. NCI’s CAM Expenditures FY 2003-2006* 

Millions 

$128,671,113 $140	 $121,076,919 $123,076,167 $119,900,000 

$120 

$100 

$80 

$60 

$40 

$20 

2003 2004 2005 2006 

* Includes grants, cooperative agreements, intramural projects, and contracts. 

Regarding grants and cooperative agreements, only includes those for which NCI 

is the primary funding IC and excludes training grants (T’s, F’s, K’s, and R25s). 

Breakdown by Major CAM Therapy Category 

In FY 2006, NCI performed or supported research 

addressing a variety of CAM therapies (Figure 5). 

These CAM therapies fall into seven groups: alternative medicine systems, exercise therapies, manipulative and body-based methods, mind-body interventions, nutritional therapeutics, pharmacological 

and biologic treatments, and spiritual therapies. 

(See page 4 for definitions of CAM categories.) 

The largest percentage (61.5%) of research 

funding went to projects that investigated nutritional 

therapeutics, which can be further broken out into 

subcategories of 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). Figure 6 shows the distribution of projects 

by the subcategories of nutritional therapeutics. 

FIGURE 4. NCI’s CAM Research Projects FY
 

2006 by Research Type*
 

Prevention 

$83,514,540 

67.85% 

Treatment 

$26,003,916 

21.13% 

Symptom/Side-Effect 

Management 

$9,072,309 

7.37% 

Epidemiology 

$4,142,826 

3.37% 

Conference 

$342,576 

.28% 

Total: 

(461 Projects) 

* Includes grants, cooperative agreements,	 $123,076,167 

intramural projects, and contracts. 

NCI CAM Annual Report 2006 23 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

FIGURE 5. NCI CAM Therapies—FY 2006* 

61.6% 19.7% 5.6% .5% 

Nutritional Pharmacological Mind-Body Manipulative & 

Therapeutic and Biologic Interventions Body-based 

$75,859,906 Treatments $6,835,368 Methods 

$24,324,808 $607,356 

1.4% 5.8% .8% 4.6% 

Alternative 

Medical Systems 

$1,707,311 

Exercise 

Therapies 

$7,140,027 

Spiritual 

Therapies 

$948,684 

Miscellaneous 

$5,652,707 

* Includes grants, cooperative agreements, intramural projects, and contracts. 

FIGURE 6. NCI’s FY 2006 CAM Nutritional 

Therapies Projects 

Bioactive Food 

Chemicals 

$19,007,708 

25% 

Vitamins 

$15,345,878 

20% 

Minerals 

$13,585,193 

18% 

Food 

$12,760,552 

17% 

Dietary Regimens 

$12,015,588 

16% 

Fat 

$3,144,986 

4% 

Total: 

$75,859,906 

Breakdown by Cancer Type 

The research projects that make up NCI’s FY 

2006 CAM research portfolio address 20 categories 

of cancer types. Among the various categories, 

prostate, breast, colorectal, and lung cancers 

received the largest amounts of cancer CAM 

research funding. Almost half (46%) of NCI’s 

cancer CAM research funding was allotted for 

multiple types of cancer within the same project. 

For a complete listing of the cancer type categories 

and estimated funding amounts, please see 

Figure 7 below. 

FIGURE 7. NCI CAM Research Projects 

FY 2006 by Cancer Type 

Bladder $731,318 

Brain $538,357 

Breast $14,788,877 

Cervical $2,645,072 

Childhood Cancer $365,561 

Colorectal $11,564,397 

Endometrial $67,174 

Esophageal $928,081 

Gastric $337,024 

Head and Neck $938,960 

Kidney $539,617 

Liver $601,364 

Lung $6,115,562 

Melanoma $516,509 

Multiple Myeloma $25,721 

Muliple Types $56,313,158 

Ovarian $136,170 

Pancreatic $1,269,592 

Prostate $18,861,790 

Skin. Non-Melanoma $5,791,863 

TOTAL: $123,076,167 

24 NCI CAM Annual Report 2006 
MAJOR ACCOMPLISHMENTS IN 2006 

Fiscal Year 2006 saw the release of major findings which for the first time offer compelling 

evidence to suggest that regular physical activity in the months following treatment may decrease 

the risk of cancer recurrence and death from colorectal cancer. The Women’s Health Initiative 

(WHI) Dietary Modification prevention study also showed that reducing dietary fat and increasing 

fruits, grains, and vegetables may reduce risk of invasive breast cancer in some women. 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

MAJOR ACCOMPLISHMENTS IN 2006 

Studies Suggest Exercise Improves 


Colorectal Cancer Outcomes 


Two new prospective, observational studies offer 

compelling evidence to suggest regular physical activity in the months after treatment may decrease the 

risk of recurrence and death from colorectal cancer. 

In the studies, patients with early- to laterstage colorectal cancer (no distant metastases) 

who engaged in regular activity after diagnosis 

had a lower likelihood of cancer recurrence and 

mortality by 40% to 50% or more compared with 

patients who engaged in little to no activity. 

Published in the July 6, 2006 issue of the Journal 

of Clinical Oncology, the studies’ results showed outcomes from exercise held true regardless of physical 

activity levels before cancer diagnosis or other factors 

that predict recurrence risk, such as the number 

of nearby lymph nodes harboring cancer cells. 

The results, said the studies’ lead author, Jeffrey 

A. Meyerhardt, M.D., M.P.H., of the Dana-Farber 

Cancer Institute, may offer insight into why some 

colorectal cancer patients who receive standard-ofcare treatments, including surgery and adjuvant 

chemotherapy, have recurrences, and some don’t. 

“One assumption has always been that it must 

be something about the molecular makeup of 

their tumor,” he said. “This study implies that 

there are some lifestyle factors that may also have 

a significant effect on [treatment] outcomes.” 

The first study, an NCI-sponsored clinical 

trial led by the Cancer and Leukemia Group B 

cooperative group, compared two adjuvant 

chemotherapy regimens in 832 patients with stage 

III colorectal cancer. 

Four and fourteen months after having their 

tumors surgically removed, well after adjuvant therapy was completed, participants provided details 

about their diet and physical activity via a selfadministered questionnaire. Only data from the 

second questionnaire were considered in the 

analysis. Researchers converted the reports of 

physical activity (ranging from jogging to flights of 

stairs climbed) to metabolic equivalent task (MET) 

hours. For example, walking at a moderate pace 

for an hour is equivalent to three MET hours. 

Compared with patients who reported less than 

three total MET hours per week, those reporting 

18 to 26.9 and 27 or more MET hours weekly 

had their risk of death from colorectal cancer 

reduced by 49% and 45%, respectively. In other 

words, six or more hours a week of walking at a 

moderate pace was associated with better outcomes. 

The second study followed a cohort of 573 

participants in the Nurses’ Health Study who, 

during the course of the study, were diagnosed 

with colorectal cancer. 

Compared with participants reporting less 

than three MET hours of activity per week, those 

reporting 18 or more had their risk of death from 

colorectal cancer cut by 61% and their risk of 

death from any cause reduced by 57%. 

In an accompanying editorial, Dr. Wendy 

Demark-Wahnefried of Duke University Medical 

Center noted that the risk reductions seen in these 

studies – as well as strikingly similar results reported 

last fall from a study of women with early-stage 

breast cancer – parallel “that of trastuzumab (Herceptin) for HER 2-positive breast cancer patients.” 

Julia Rowland, Ph.D., head of the NCI Office 

of Cancer Survivorship, said these findings add to 

the evidence base on physical activity and cancer 

outcomes. “They suggest that the time may be ripe 

to launch a randomized clinical trial of physical 

activity after cancer treatment,” she continued. 

In March 2006, the NCI-sponsored workshop Feasibility of a Physical Activity, Weight 

Control Trial to Prevent Breast Cancer examined 

the rationale for and issues related to designing a 

physical activity intervention in the context of 

a primary prevention trial and also for a trial to 

prevent breast cancer recurrence and death in 

survivors. NCI also contributed to the American 

Cancer Society’s guidelines on “Nutrition and 

Physical Activity During and After Cancer Treatment” published in the November/December 

2006 issue of the journal CA. 

26 NCI CAM Annual Report 2006 

NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

MAJOR ACCOMPLISHMENTS IN 2006 

Low-Fat Diet May Have Small Impact on
 

Breast Cancer in Women
 

Results from the Women’s Health Initiative 

(WHI) Dietary Modification (DM) prevention 

study show that reducing dietary fat and increasing 

fruits, grains, and vegetables may reduce risk of 

invasive breast cancer in some women, but has no 

effect on invasive colorectal cancer. Although 

more than 19,500 postmenopausal women followed 

the modified diet, the overall breast cancer risk 

reduction of 9% was not statistically significant 

after an average of 8.1 years. Women whose diets 

were highest in fat before they entered the study, 

however, were 22% less likely to develop breast 

cancer than the comparison group. 

Ross L. Prentice, Ph.D., of the Fred Hutchison 

Cancer Research Center in Seattle and colleagues 

write that the risk reduction seen in this and other 

subgroups “would not be expected if the intervention had no effect on breast cancer risk.” 

Citing other trends in the data in favor of DM, 

they note the benefit increased to 15% among 

women who most closely followed the dietary 

regimen. Also, citing the small impact of DM on 

breast cancer, which begins to occur after about 4 

years and appears to be increasing with time, the 

authors note that “the health implications of a 

low-fat dietary pattern may take years to be fully 

realized.” In an accompanying editorial, Aman U. 

Buzdar, M.D., from the University of Texas M.D. 

Anderson Cancer Center said the study is another 

indication that breast cancer oncologists “are 

beginning to understand which approaches may 

be effective for particular subsets of patients.” 

Leslie Ford, M.D., of NCI’s DCP, noted that, 

“Breast cancer is an exceedingly complex disease. 

The more we learn about the molecular underpinnings of the disease, the better we will understand 

how a healthy eating pattern and exercise may 

contribute to a reduction in risk for some women.” 

Regarding the colorectal study, lead author 

Shirley A.A. Beresford, Ph.D., of the University 

of Washington in Seattle and colleagues also say 

that the currently planned, longer follow-up 

studies “may reveal delayed benefit,” although, 

unlike the breast cancer study, “no time trends 

...have been seen.” 

The WHI DM study is the largest randomized 

controlled clinical trial of low-fat dietary interventions ever conducted. Results were published 

in the February 8, 2006, Journal of the American 

Medical Association. 

This article was originally published in the 

NCI Cancer Bulletin, February 7, 2006, Volume 3, 

Number 6. (http://www.cancer.gov/ncicancer 

bulletin/NCI_Cancer_Bulletin_020706/page5) 

28 NCI CAM Annual Report 2006 
ADDRESSING NCI’S STRATEGIC AREAS WITH EXTRAMURAL RESEARCH 

The remaining research highlights are selected from the 461 CAM research projects that NCI 

supports at laboratories throughout the 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. Abstracts for the 

research projects featured in the report can be found by searching the NIH Computer Retrieval 

of Information on Scientific Projects (CRISP) database at http://crisp.cit.nih.gov. 
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. 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

UNDERSTANDING THE CAUSES AND MECHANISMS OF CANCER 

Antioxidants and Chemotherapy:
 

Help or Hindrance?
 

Division of Cancer Control and Population Sciences 

According to recent studies, such as the Women’s 

Healthy Eating and Living (WHEL) Study, as 

many as 50% to 60% of cancer patients take 

vitamins or other nutritional supplements during 

treatment, and up to 20% use supplements containing high doses of antioxidants. Traditionally, 

doctors have cautioned patients not to take 

antioxidants during chemotherapy, because many 

anticancer drugs kill tumor cells by forming 

oxygen-based compounds that damage DNA. 

It is not clear, however, if antioxidants do 

actually interfere with the effects of chemotherapy. 

In fact, said Christine Ambrosone, Ph.D., chair of 

Epidemiology and Cancer Prevention at Roswell 

Park Cancer Institute, “Some preclinical and 

animal data have shown that when antioxidants 

are given with chemotherapy, they decrease toxicity 

so that more of a drug can be given. They also 

increase efficacy – the antioxidants with the 

chemotherapy agent work better than the chemotherapy agent alone.” 

“There haven’t been any large studies conducted in very well-controlled environments 

where everybody is getting the same treatment 

agent and followed up carefully,” Ambrosone 

added. “The preclinical studies evaluating effects 

of antioxidants given with chemotherapy have 

usually used very high doses, so we don’t know 

what, if anything, happens when people take 

supplements at the levels commonly available.” 

In September 2006, Ambrosone and her 

colleagues received NCI funding* to begin a 

prospective observational study of antioxidants 

and chemotherapy as part of a clinical trial being 

conducted by the Southwest Oncology Group 

(SWOG). That trial will randomly assign women 

with invasive breast cancer to one of four 

chemotherapy regimens, comparing different 

doses, intensities, and schedules of the chemotherapy drugs cyclophosphamide, adriamycin, 

and paclitaxel. 

For the antioxidant study, participating women 

will fill out a detailed questionnaire reporting the 

composition and dosage of any multivitamins 

taken regularly, as well as the use of additional 

supplements and other complementary and alternative treatments. The women will provide this 

information before starting chemotherapy, after 

treatment, and then yearly during follow-up for 

the main clinical trial. 

The investigators will also look at the contribution of lifestyle factors, including physical 

activity, alcohol consumption, and smoking, and 

perform laboratory studies to determine if genetic 

make-up, particularly related to protection from 

oxidative stress, has any effect on relationships 

between supplement use and treatment outcomes. 

While results from this study can only be 

applied to women given the specific chemotherapy drugs tested in the SWOG clinical trial, 

“almost all women treated for breast cancer are 

given some combination of cyclophosphamide, 

adriamycin, and a taxane,” Ambrosone explained. 

“So the results would apply to a very large patient 

population.” 

Isis S. Mikhail, M.D., Dr.P.H., with NCI’s 

DCCPS commented: “This is a very interesting 

study by Dr. Ambrosone that could answer a challenging question regarding the association 

between use of antioxidant supplements, cancer 

treatments outcome, and the contribution of 

genetic and lifestyle factors. This study fits very 

well with the DCCPS portfolio, and following up 

this group of women participating in the SWOG 

trial prospectively before, during, and after they 

start their chemotherapy regimen is an effective 

model and could have valuable results that can be 

translated to benefit many cancer patients.” 

*Grant number: 1R01CA116395-01A1 

NCI CAM Annual Report 2006 31 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

UNDERSTANDING THE CAUSES AND MECHANISMS OF CANCER 

Calcium and Vitamin D 


May Help Prevent Colorectal Cancer
 

Division of Cancer Control and Population Sciences 

Colorectal cancer causes more deaths in the United 

States than any other cancer except lung. Roberd M. 

Bostick, M.D., M.P.H., a professor at Emory 

University in Atlanta, believes part of the reason is 

that we no longer eat like people did in prehistorical 

times. “We consume very little calcium and vitamin 

D by evolutionary standards,” he said. Bostick’s lab 

is currently studying whether those dietary components could be used to prevent adenomatous polyps, 

a precursor of most cases of colorectal cancer. 

“We’ve made huge progress in preventing 

heart attacks,” explained Bostick. “By taking steps 

to reduce blood pressure and cholesterol, you can 

directly reduce risk. Treat the biomarker (high 

cholesterol), and you may stop the disease before it 

fully develops.” His lab is working on a similar 

approach to colorectal cancer. In an NCI-supported 

research study*, they recruited patients who have 

had adenomatous polyps surgically removed and 

are thus at high risk of recurrence. 

Patients take pills twice a day receiving calcium, 

vitamin D, both, or a placebo that contains neither. 

Biopsies of their rectal tissue will be examined 

after one, three, and five years to see if any differences at the lining of the colon emerge between 

the various groups. In addition, patients will 

undergo colonoscopies three and five years after 

entering the study to see if they have developed 

any new polyps. “If we could show that calcium 

and/or vitamin D can treat the biomarkers and 

prevent these warning-sign polyps from developing, 

we would have a bona fide medical strategy to 

prevent colorectal cancer,” said Bostick. 

While calcium has been shown to have a moderately protective effect in a few studies, “we need to 

know better how and why,” explained Bostick. Some 

evidence suggests that calcium’s protective effect is 

greater in people with fairly high storage levels 

of vitamin D, but the studies have usually been 

confounded by the fact that both dietary substances 

often occur together, such as in dairy products. This 

new clinical trial will tease apart their separate impact 

by controlling for other dietary sources – many 

foods are fortified with vitamin D in the United 

States – and by checking circulating blood levels 

of vitamin D that can be influenced by sunlight. 

“We’re trying to develop meaningful markers 

in the tissue by looking at a number of genes that 

produce the enzymes we know to be part of the 

pathways that metabolize the calcium and vitamin 

D,” Bostick said. Vitamin D is not only manufactured but also removed from the body by different 

genes, so they also want to measure actual blood 

levels, not merely intake. “It makes sense that the 

active vitamin D in the body is a balance between 

these two processes,” he noted. 

The researchers also believe that the amount 

of proteins produced may be as important as 

genes simply turning on or off, and these protein 

levels could be influenced by other factors. “We 

hope to develop a fuller picture that includes 

genes, proteins, and blood levels of the nutrients,” 

Bostick said. From that picture could emerge new 

blood tests which would better identify people at 

high risk for colorectal cancer. “Since only about 

6% of people get the disease and die from it, 94% 

of those receiving colonoscopies may not really 

need them,” he noted. The public health impact 

would be dramatic, getting those at greater risk 

into screening and treatment earlier, and saving 

money on costs and risks associated with periodic 

colonoscopies among low-risk individuals. 

NCI’s Program Director for the study Virginia 

W. Hartmuller, Ph.D., R.D., commented, “Dr. 

Bostick’s study is important to NCI’s Diet/Nutrition 

Cancer Epidemiology research portfolio since he is 

examining whether the formation and degradation of 

the active form of vitamin D provides a critical focal 

point underlying the development of colon cancer.” 

She noted the NCI-sponsored meeting Vitamin D 

and Cancer: Current Dilemmas/Future Needs in 

May 2007 discussed research in this critical area. 

*Grant number: 1R03CA121873-01 

32 NCI CAM Annual Report 2006 

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 cancer-causing processes through early 

medical intervention. 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

ACCELERATING PROGRESS IN CANCER PREVENTION 

Lycopene Studied for the 


Prevention of Lung Cancer
 

Division of Cancer Prevention 

While observational studies have shown a protective effect against lung cancer from a diet high in 

fruits and vegetables, isolating specific plant compounds for use as chemopreventive agents has 

proven difficult. Beta carotene, and other related 

compounds called carotenoids, showed promise 

in preventing lung cancer in animal models; however, clinical trials in humans actually found an 

increase in lung cancer incidence in smokers given 

the compounds. 

New carotenoid chemoprevention studies are 

now focused on better understanding biological 

activity, dose safety, and interactions with the 

byproducts of cigarette smoke before progressing 

to human trials, explained Xiang-Dong Wang, 

M.D., Ph.D., professor and co-leader of the Cancer 

Prevention Program at the Tufts University Cancer 

Center. He is currently studying lycopene, a major 

carotenoid from tomato and tomato products, in a 

model of lung cancer in ferrets*. 

“We’re trying to answer three main questions,” 

said Wang. “First, what is the role of lycopene in 

lung cancer chemoprevention? Second, what is 

the optimal dose in terms of lung cancer prevention 

and safety? Lastly, we’re trying to understand the 

mechanism of how lycopene and its metabolites 

may help to protect against lung cancer.” 

The ferret provides an excellent animal 

model for the study of lung cancer and of 

lycopene as a chemopreventive agent in humans. 

Ferrets and humans both absorb lycopene intact, 

and the tissue distribution and metabolism of the 

compound are also similar between the species. 

Most animals, including mice and rats, must be 

given relatively huge doses of carotenoids to 

observe any biological effect. The use of such 

megadoses in laboratory models might have 

caused unnecessarily high, even dangerous doses 

to be chosen for previous human chemoprevention trials of carotenoids, explained Wang. 

Ferrets exposed to cigarette smoke and lycopene 

can be expected to provide a more accurate 

estimation of a safe dose for human trials. 

Because specific metabolites have been implicated in the increased incidence of lung cancer in 

smokers given beta carotene, Wang and his 

colleagues are performing both laboratory experiments and animal testing to understand the 

biological activity of lycopene metabolites. Their 

experiments have already demonstrated that 

lycopene can be converted into a highly biologically 

active molecule called apo-10’-lycopenoic acid. 

Additional work from Wang’s laboratory will 

focus on identifying biomarkers that can be used 

in human clinical trials to track the biological 

activity and the metabolism of lycopene. 

Marjorie Perloff, M.D., with the NCI DCP, 

called Wang’s research important, because it spans 

the spectrum from epidemiology trials in humans, 

back to animal research, “and, hopefully, then 

back again to human studies.” It is also significant, 

she adds, because lycopene is currently being used 

by consumers as a nutritional supplement, but 

could later be more carefully developed as a pharmaceutical agent, if that is warranted by the final 

results from Wang’s research and from other 

scientific studies. 

*Grant number: 1R01CA104932-01A2 

Dr. Wang is currently 

studying lycopene, a major 

carotenoid from tomato and 

tomato products, in a model 

of lung cancer in ferrets. 

NCI CAM Annual Report 2006 35 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

ACCELERATING PROGRESS IN CANCER PREVENTION 

Concentrated Vitamin D 


May Slow Prostate Cancer
 

Division of Cancer Biology and Office of Centers, Training and Resources 

Prostate cancer is the second-leading killer of 

men in America. In a series of related studies, 

scientists have shown that vitamin D may have a 

significant role to play in slowing progression of 

the disease. 

“Currently, docetaxel is the most potent 

chemotherapy drug we have for prostate cancer,” 

explained Tomasz Beer, M.D., director of 

Prostate Cancer Research at the Oregon Health 

and Science University Cancer Institute in 

Portland, Oregon. “We have found a promising 

companion agent that appears to enhance the 

impact of docetaxel, an activated form of vitamin 

D known as calcitriol. In an NCI-supported study 

in 2003, we showed it to be safe when given once 

a week at a dose that is larger than would ever be 

found naturally.” 

While researchers continue to test that drugsupplement combination in a large, randomized, 

controlled trial for prostate cancer, Beer is now 

hard at work, under a grant from NCI*, trying to 

figure out exactly how calcitriol helps docetaxel kill 

prostate cancer cells. He is also examining what 

role it could potentially play as an adjunct to other 

treatments, possibly for other types of cancer. 

“We’ve found a promising gene, which we’re 

hoping might develop into a new therapeutic 

target,” Beer said. The gene belongs to the 

“homeobox” family. As a group, homeobox genes 

have been known as one of the main ways that 

growing organisms figure out how to segment 

themselves into different functional regions, 

which in turn form limbs and other structures. 

Calcitriol appears to turn off one of the 

homeobox genes, both in patients with prostate 

cancer and in certain human prostate cancer cells 

in the lab, Beer found. As a result, the cancer cells 

die – a fate that applies to most normal cells in the 

body but which many cancers are able to avoid. 

Calcitriol may somehow be reversing this unnatural 

“immortality” of cancer cells, allowing them to 

die a programmed death like the rest of the body’s 

cells – a process that scientists call “apoptosis”. 

Beer and his colleagues are conducting a 

series of experiments in mice that should begin to 

explain calcitriol’s effects on homeobox genes in 

prostate cancer cells**. This includes testing the 

gene’s impact on artificially-induced tumors, both 

in the prostate and elsewhere. Ultimately, they 

hope to demonstrate that this homeobox gene is 

a target that calcitriol can switch off in order 

to slow down or even prevent the growth of 

prostate cancer. 

*Grant numbers: 1R21CA113380-01A1 and 

**5P30CA069533 

A computer-generated molecular model of calcitriol, 1,25-dihydroxycholecalciferol, the biologically active form of 

vitamin D, with carbon atoms shown in blue, hydrogens in white, and oxygen in red. 

36 NCI CAM Annual Report 2006 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

ACCELERATING PROGRESS IN CANCER PREVENTION 

Improving Cancer Prevention Strategies
 

Using the Biological Clock
 

Division of Cancer Prevention 

Because the Earth revolves completely around its 

axis every 24 hours, it makes sense that this daily 

(circadian) cycle has left its imprint on the evolution 

of life and the biology of all living organisms. The 

research field of chronobiology has developed 

over some four decades to pursue the implications 

of this biological clock, particularly on medical 

treatments. 

“We refer to it as chronotherapeutics,” said 

Jack Burton, M.D., an investigator in immunology 

and oncology at the Center for Molecular 

Medicine and Immunology at the Garden State 

Cancer Center in Belleville, New Jersey. “It 

involves administering treatment as a function of 

the body’s circadian rhythms, in an effort to make 

certain cancer treatments more effective and to 

cause fewer side effects.” 

“Both laboratory and clinical research have 

left little doubt that the timing of treatment matters,” Burton believes. A number of studies have 

already shown that patients do better when their 

treatments are scheduled at certain times of their 

daily cycle. 

The body’s internal “clock” may be controlled 

by the brain, but cells in many tissues have independent circadian rhythms as well, including, as it 

turns out, tumors. In earlier research, Burton and 

colleagues showed in a mouse model of breast 

cancer that more than twice the amount 

of the drug celecoxib (Celebrex®) is safe and well 

tolerated when given at a specific time of day, 

leading to a greater inhibition of tumor growth 

and less toxicity to the animal. 

“The body’s internal rhythms as set by its own 

biological clock appear to affect all phases of 

treatment – surgery, radiotherapy and particularly 

chemotherapy, as well as the side effects that follow 

them,” explained Burton. 

The next big area for circadian rhythm 

research may well be cancer prevention. Burton’s 

lab is building on the principles and successes of 

earlier work in chronotherapeutics. “Several nutritional substances have shown promise in their 

preventive effects on the development of various 

cancers in people,” he noted, including, an ingredient in the spice turmeric, vitamin D, selenium, 

and green tea. His first studies will test selenium 

and a purified extract of green tea. 

“We hope to establish a robust proof of principle in animal models that will provide key preliminary data to design appropriate human studies,” 

Burton said. In one study, mice were injected with a 

prostate cancer cell line, which in several weeks produces visible tumors. “As with classical therapeutic 

agents, our earlier results in this model demonstrate 

that preventive agents also inhibit the growth of 

experimental prostate tumors differently according 

to circadian delivery times,” he reported. 

The current studies use a similar mouse 

model to evaluate how chronobiology might 

influence the preventive effects of selenium and 

green tea*. Part of the study will test how well 

these preventive agents reach the prostate and 

other tissues. “We will collect all of these specimens into a tissue bank for use in future genomic 

and proteomic studies to understand the mechanisms by which these agents prevent cancer and 

to better understand any resulting side effects,” 

Burton said. 

*Grant number: 1R21CA113470-01A2 

NCI CAM Annual Report 2006 37 
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 well-tolerated, individualized therapies that are tailored to specific features 

of a patient’s cancer. 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

DEVELOPING EFFECTIVE AND EFFICIENT TREATMENTS 

Ginseng Studied as Possible 


Breast Cancer Treatment
 

Division of Cancer Treatment and Diagnosis 

Herbal supplements like ginseng have been in use 

for centuries in Asia, but U.S. researchers and 

government agencies have been cautious about 

certifying them for use in medical practice, especially for cancer. “And yet the evidence continues 

to mount that ginseng has anticancer properties,” 

said Laura Murphy, Ph.D., an associate professor 

in the Department of Physiology at Southern 

Illinois University in Carbondale. 

“Ginseng is a virtual drugstore,” explained 

Murphy, referring to some 20 ginsenosides, bioactive phytochemicals found in the American 

species of ginseng root. This rich diversity is both 

good and bad news. Each of the ginsenosides 

may have its own pharmacological effect, which 

reflects one of the recurring dilemmas in using 

botanicals as medicine. When people buy unregulated dietary supplements or even whole roots, it 

is hard to know what combination of ginsenosides they are getting and in what strengths. In 

addition, Asian ginseng (Panax ginseng) and 

American ginseng (Panax quinquefolius) have different concentration profile of ginsenosides, so it 

is expected they would show different effects on 

cancer cells. Murphy’s lab has been working on 

this dilemma by developing reliable methods to 

evaluate the more important of these ginsenosides, 

alone and in combination. 

Murphy’s current NCI-supported work* is 

focused on the Rg3 and Rh2 ginsenosides which 

are thought to be especially effective against cancer 

cells. She continues the effort to tease out the 

specific biological action for each of these ginseng 

components. In animal and cell studies, “we 

showed they slow down tumor cell progression by 

inducing more of the p21 protein, an important 

cell cycle regulator involved in cancer cell proliferation,” Murphy reported. By adding a third ginsenoside known as Rc, they developed a “3-ginsenoside 

cocktail” that potently inhibits the proliferation of 

a human breast cancer cell line known as MCF-7. 

The cocktail also selectively inhibits and kills cancer 

versus normal mammary cells. 

“We’re finding that not all ginseng components 

are equal,” commented Murphy. “For example, 

ginsenoside Rg1 completely counteracted MCF-7 

cell inhibition induced by other anticancer ginsenosides. So while some of the anticancer ginsenosides work together, others appear to undermine 

their efficacy.” This line of research may lead to 

the characterization of an effective or a biologically 

well defined combination of ginsenoside mixtures 

that could be used to complement standard treatments of breast cancer. More research into the 

mechanism of action of ginseng’s pharmacologically 

active ingredients is needed. 

“Complementary ginseng use has gained credibility in human studies,” Murphy noted. Research 

published in the April 1, 2006 American Journal of 

Epidemiology has shown that ginseng usage, along 

with standard treatments, increases both survival 

and quality of life in breast cancer patients. 

However, Murphy cautioned that it is premature 

to unequivocally recommend that patients take 

ginseng during cancer treatment. “Ginseng use has 

not been studied with the more modern 

chemotherapy medications, and it could potentially 

interfere or interact with some of them,” she 

added. Still, she is hopeful that “eventually ginseng 

may be validated for prevention as well as in the 

complementary treatment for some cancers.” 

Yali Fu, Ph.D., of NCI’s DCTD noted, “The 

work done by Dr. Murphy is significant, because 

pure ginsenosides are being tested in cancer cells 

to see their effects. This is a step in the right 

direction for providing direct molecular evidence 

on the effects of ginsenosides. NCI continues to 

support this kind of research in its mission to find 

better treatment for cancer. Further studies are 

needed in animal models and human testing to 

validate the effectiveness of ginseng products.” 

*Grant number: 1R21CA121074-01 

NCI CAM Annual Report 2006 39 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

DEVELOPING EFFECTIVE AND EFFICIENT TREATMENTS 

Noni Juice Studied for 


Prevention of Breast Cancer
 

Division of Cancer Prevention 

The development of cancer (carcinogenesis) is recognized to be a multistage process. The occurrence 

of DNA adducts represents an early biomarker of 

exposure to cancer-causing agents and the likelihood that the cancer process has been initiated. 

A clinical trial with Morinda citrifolia, better known 

as “noni juice” for lung cancer prevention in 340 

smokers provided some interesting findings. 

After one month, noni juice significantly 

reduced the binding of aromatic adducts to DNA 

in smokers, raising the possibility that it might also 

reduce cancer risk. “DNA adducts are a good 

marker for very early carcinogenesis and cancer 

prevention,” said Mian-Ying Wang, M.S., M.D., 

who has been exploring the use of noni juice for 

the prevention of cancers for eight years. “If noni 

supplements are able to block carcinogen binding 

to DNA, it could prevent carcinogenesis at the 

initiation stage.” 

“Because noni juice is a strong antioxidant 

and an anti-inflammatory nutritional supplement, 

we wanted to know if it can help prevent cancer 

in another model,” Wang explained. To test her 

hypothesis, Wang received a developmental grant 

from NCI to study whether noni juice can help 

prevent carcinogen-induced tumor formation in 

an animal model of breast cancer. 

Her current investigations use the carcinogenic agent dimethylbenz(a) anthracene (DMBA) 

to induce mammary cancer*. In her studies, rats 

received water or water supplemented with up to 

10% noni juice. Preliminary results revealed that 

those animals given 5% noni juice fortified water 

had the lowest incidence of tumor formation 5 

months after exposure to DMBA. 

*Grant number: 1R21CA121682-01A2 

A Noni Flower. The Noni plant bears a fruit which can be eaten and is sometimes used for natural medicinal purposes. 

40 NCI CAM Annual Report 2006 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

DEVELOPING EFFECTIVE AND EFFICIENT TREATMENTS 

Studying the Effects of Vitamin E and Soy
 

During Radiation for Prostate Cancer
 

Division of Cancer Prevention 

After being diagnosed with cancer, many individuals search for information and make decisions 

about their lifestyles that they believe will benefit 

their health and their cancer treatments. Some 

men with prostate cancer will decide to take 

dietary supplements such as vitamin E and soy 

products containing substances called isoflavones. 

These supplements have antioxidant properties, 

and both are being studied for their potential 

benefits in men with prostate cancer. 

Some medical oncologists are concerned that 

these antioxidants may actually interfere with radiation therapy for prostate cancer. They point out 

that radiation kills cancer cells in part by creating 

oxygen radicals, and antioxidants, including vitamin E and soy isoflavones, may work against the 

creation of the oxygen radicals. 

“We know that prostate cancer patients are 

taking these supplements, but we don’t know 

whether the patients should be taking them if they 

are having radiotherapy,” cautioned Kathleen 

Shiverick, Ph.D., of the Department of Pharmacology and Therapeutics at the University of 

Florida, Gainesville. She has been exploring this 

question in cells in the laboratory. 

Now her team is using NCI* funding to study 

the question in mice. The researchers are investigating whether vitamin E and soy isoflavones may 

enhance the toxicity of radiotherapy or may actually 

interfere with the radiotherapy in mice. A second 

study question is whether exposing prostate cancer 

cells to antioxidants after radiation therapy might 

slow the growth of cells that survive radiation. 

In recent years, Shiverick and others have 

done experiments using prostate cancer cells, with 

encouraging results. When prostate cancer cells 

were exposed to physiologically relevant levels of 

these two antioxidants prior to radiation therapy, 

the antioxidants sensitized the cancer cells to the 

radiation. This meant that fewer cells survive the 

radiation. Each antioxidant—soy and vitamin E— 

decreased the survival of cells following radiation, 

and there was an additive effect with the combination of radiation and the two antioxidants. 

Interestingly, adding antioxidants to the cells 

that survived radiation further slowed the growth 

of cells. “For the cells that survived irradiation, 

their growth was much more inhibited,” reported 

Shiverick. Each antioxidant alone had a significant 

effect, and the two together had the dramatic 

effect of preventing any cells from surviving. 

Dr. Shiverick cautions that an animal study 

cannot be designed to directly distinguish between 

the antioxidant, hormonal, or phytoestrogenic 

effects of isoflavones because of the complex 

interactions that occur between the host mouse 

and the tumor microenvironment, especially in 

the case of hormonally affected cancers. 

“We expect that the phytoestrogenic effect 

will be clearly seen, because the mice are reported 

to be able to convert the soy isoflavone daidzein 

to equol, which is a more potent phytoestrogen 

than genistein,” says Dr. Shiverick. 

Her team chose the combination of Vitamin E 

and soy for this study because their experiments with 

cultured prostate cancer cells have identified different cell-signaling mechanisms that are involved 

in the growth inhibitory effects of these two agents, 

respectively. They have found additive growth 

inhibitory effects of the Vitamin E/soy combination at low concentrations, as well as a marked 

interaction with irradiation in the cell culture model. 

Completion of the mouse studies will take 

several years. In the meantime, many prostate 

cancer patients will take antioxidants without 

knowing how they might affect their therapies. 

“People like to have some degree of control over 

their course of treatment, and they like to think 

that nutritional supplements will be beneficial for 

them,” noted Shiverick. It is hoped that these 

mouse studies will begin to provide information 

to help answer what has become an important 

question to many men with prostate cancer. 

*Grant number: 1R21CA102386-01A2 

NCI CAM Annual Report 2006 41 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

DEVELOPING EFFECTIVE AND EFFICIENT TREATMENTS 

Disrupting a Tumor’s Biological Clock to
 

Improve Treatment Responses
 

Division of Cancer Prevention 

Researchers often find puzzling differences in 

how well cancer patients respond to chemotherapy 

and how severely they experience side effects of 

those treatments. One explanation that is now 

being actively pursued involves a field called 

chronopharmacology. Chronopharmacology seeks 

to provide patients their drug treatments at times 

of the day and night during which their bodies’ 

biological “clocks” make the target cancer cells 

most vulnerable and when side effects will be 

minimized. 

Alec J. Davidson, Ph.D., who works at the 

Neuroscience Institute at the Morehouse College 

of Medicine in Atlanta, believes that “we can 

manipulate the body’s circadian system to inhibit 

cancer.” His lab was one of the first to show that 

tumors have their own circadian (24-hour) rhythms. 

“All cells divide and replicate, and that 

process is regulated by their circadian clock,” 

explained Davidson. “Since uncontrolled cell 

proliferation is the essential threat posed by 

carcinogenesis, we think that the internal rhythm 

that is timing that proliferation could perhaps be 

disrupted.” Earlier work by his team showed that 

the cycles in isolated tumor cells were shortened 

by as much as four hours. 

Currently, Davidson’s NCI-sponsored research* 

is focused on how the livers of rats use such 

built-in clocks to anticipate their next meal and 

how researchers might be able to manipulate this 

system to fight hepatocellular carcinoma, cancer of 

the liver. “Timing plays an important role in how 

the liver functions,” noted Davidson. Clock genes 

in that organ orchestrate rhythmic processes that 

influence digestion and elimination. “It turns out 

those rhythms are synchronized not by the time of 

day (i.e. triggered by exposure to light), but rather 

by the timing of previous food intake,” he added. 

While these digestive rhythms appear to persist in 

liver cancer, they are altered and respond less well 

to the timing signal for feeding. 

“An intriguing possibility is that the altered 

response to feeding schedules in transformed liver 

tissue relates to the result that daily meal-feeding 

actually inhibits cancer growth,” Davidson 

suggested. Research has shown that a restricted 

(low-calorie) diet “dramatically increases life span 

in many species, and probably that includes ours,” 

he continued. Mouse experiments also clearly 

show that tumors develop less aggressively when 

the host is on a restricted diet. 

“What is new here and most important is 

that the timing of food intake – not just the 

amount– has an impact on cancer,” Davidson 

explained. “Since timing regulates nearly all of 

our body’s functions, it is not surprising that the 

timing of food delivery is an important regulator 

of tumor growth.” 

The researchers will induce hepatocellular 

carcinoma and then measure how liver disease 

develops in response to restricted feeding, compared 

with rats that eat during the daytime, the nighttime, or on an irregular schedule. “We expect to 

see tumor growth respond to alterations in the 

liver’s clock, induced by these artificially created 

feeding times,” Davidson said. Such work is 

adding to a powerful foundation of evidence that 

may one day profoundly change our perception of 

the links between diet and cancer. 

*Grant number: 1R21CA116261-01A1 

42 NCI CAM Annual Report 2006 

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 evidencebased interventions that are safe, patient-centered, effective, timely, efficient, and equitable. 
 

NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

IMPROVING THE QUALITY OF CANCER CARE 

Soy Protein Studied for Men at
 

High Risk of Prostate Cancer Recurrence
 

Division of Cancer Prevention 

Some men who have surgery for prostate cancer 

– involving removal of the entire prostate gland 

or radical prostatectomy – also undergo additional 

(adjuvant) treatment with radiation therapy, 

hormone therapy, or chemotherapy. However, 

most patients with radical prostatectomies don’t 

automatically receive follow-up treatment but are 

followed closely after their operation. Before 

determining the need for additional treatment, 

doctors monitor whether a substance in the surgical 

patients’ blood, prostate-specific antigen (PSA), 

becomes detectable, which indicates a potential 

recurrence. 

Researchers are looking for new approaches 

that can be used after surgery for prostate cancer 

to reduce the risk of recurrence but have fewer 

side effects than the currently available conventional therapies. Maarten Bosland, D.V.Sc., Ph.D., 

professor of Pathology at the University of 

Illinois at Chicago and research professor of 

Environmental Medicine and Urology at the New 

York University School of Medicine, is studying 

soy protein isolate as a potential adjuvant therapy 

to prevent prostate cancer recurrence. 

“Soy isoflavones have been investigated quite 

extensively in tissue culture, and there are clearly 

effects that can be interpreted as anticancer 

effects, such as inhibition of cell proliferation, 

induction of apoptosis (cell death), and inhibition 

of angiogenesis (tumor blood supply),” said 

Dr. Bosland. One specific isoflavone – genistein – 

inhibits the activity of a group of enzymes called 

protein tyrosine kinases, which play an important 

role in the regulation of cancer cell growth. 

Under a grant from NCI*, Bosland and his 

colleagues are currently enrolling participants 

into a two-arm, randomized, placebo-controlled 

clinical trial of soy protein isolate for men who 

are at high risk for prostate cancer recurrence 

after radical prostatectomy. The investigators 

will randomly assign participants to receive either 

20 grams of soy protein isolate a day or a caseinbased placebo for two years or until cancer 

recurrence. Use of a highly sensitive test for PSA 

will allow for early detection of rising PSA levels, 

indicative of recurrence. 

The investigators are also recruiting additional participants into a related pharmacology study. 

Men scheduled for prostate cancer surgery will 

take 20 grams of soy protein isolate a day for four 

to six weeks before their operation. The investigators will then use samples from the removed 

prostate tissue to measure the concentrations of 

soy isoflavones relative to the dose given, as well 

as the activity of tyrosine kinase enzymes and 

indicators of cell proliferation, apoptosis, and 

angiogenesis, explained Bosland. “That will give 

us a biological basis to interpret the data from the 

larger trial.” 

If their trial shows a decreased risk of recurrence in patients taking the soy protein isolate, 

“this would be a non-toxic, non-burdensome 

additional treatment patients could get in the 

adjuvant setting,” said Bosland. “It’s never been 

tested in a rigorous fashion, which is why we’re 

doing this trial.” 

Howard L. Parnes, M.D., chief of NCI’s 

Prostate and Urologic Cancer Research Group, 

commented: “Completion of this trial would 

clearly advance the field of prostate cancer 

chemoprevention.” 

*Grant number: 1R01CA116195-01A1 

NCI CAM Annual Report 2006 45 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

IMPROVING THE QUALITY OF CANCER CARE 

Flaxseed and Curcumin for the Prevention of
 

Radiation-Induced Lung Injury
 

Division of Cancer Treatment and Diagnosis 

The amount of radiation that can be administered to fight a lung tumor is limited by potential 

damage to normal tissue, which includes inflammation and scarring. Such a condition is called 

pneumonopathy. 

“A safe and effective biologic radioprotector 

would be extremely useful” in the prevention of 

radiation-induced pneumonopathy, said Dr. Melpo 

Christofidou-Solomidou, associate professor of 

medicine at the University of Pennsylvania. She 

and her colleagues are currently examining 

dietary supplementation with the well-known 

grain flaxseed or curcumin—an antioxidant agent 

derived from the spice turmeric—as potentially 

protective therapy against radiation-induced lung 

damage in a mouse model.* 

These natural compounds may activate a 

cellular antioxidant pathway called Nrf2/ARE. 

“The Nrf2/ARE pathway is a ‘master switch’ 

that, when triggered by agents such as lignans, 

bioactive compounds of flaxseed or curcumin, 

initiates a cascade of downstream events that 

regulate the antioxidant and overall protective 

machinery of the cell,” explained ChristofidouSolomidou. These antioxidant effects would 

protect normal cells but not cancer cells, due to 

the different regulatory pathways active in the 

two types of cells. 

Preliminary data from their project have 

been promising. In one experiment, mice fed a 

diet supplemented with 10% flaxseed for three to 

four weeks before receiving radiation therapy to 

the thorax did not show a decrease in early lung 

inflammation. However, they had significantly 

decreased late lung fibrosis and increased survival. 

An associated experiment showed that activation 

of the Nrf2/ARE pathway and expression of 

associated enzymes was increased in mice fed a 

10% flaxseed diet for three weeks. 

Mice fed a diet supplemented with 5% curcumin for two weeks before radiation therapy 

and then switched to a normal diet after treatment also had significantly less lung fibrosis after 

radiation therapy. Survival at four months after 

treatment was 45% for mice receiving curcumin 

supplementation compared to 23% in mice fed a 

normal diet. 

The investigators presented this preliminary 

data at the Experimental Biology Annual Meeting 

in spring 2007. Additionally, they hope to begin 

a small, exploratory pilot trial of flaxseed or 

curcumin supplementation to prevent pneumonopathy in lung cancer patients scheduled 

to receive a standard three-month course of 

fractionated radiation therapy. The pilot study 

will evaluate the feasibility of a full-scale trial by 

determining the metabolism of the compounds 

in humans and demonstrating the ability to measure 

changes in radiation-induced toxicity in this patient 

population. 

*Grant number: 1R21CA118111-01 

46 NCI CAM Annual Report 2006 

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. 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

IMPROVING THE QUALITY OF LIFE FOR CANCER PATIENTS, SURVIVORS, AND THEIR FAMILIES 

Tai Chi Chih Effects on Insomnia 


Studied in Breast Cancer Patients
 

Division of Cancer Control and Population Sciences 

Many breast cancer patients and survivors suffer 

from chronic fatigue and insomnia which impacts 

their quality of life and may negatively affect their 

long-term survival. Given the well-known drawbacks of sleep medications, especially among 

older and sicker patients, there is a great need for 

behavioral interventions that have proven highly 

effective in the treatment of insomnia. However, 

these interventions have yet to be studied widely 

in cancer patients. 

The ancient Chinese slow movement meditation practice of Tai Chi Chih (TCC) is a promising 

candidate for remedying sleep impairments, leading Michael R. Irwin, M.D., at the University of 

California at Los Angeles (UCLA) medical 

school, to initiate the first randomized, controlled 

clinical trial of the effects of TCC on sleep 

outcomes in breast cancer survivors. “There is 

a tremendous need for the treatment of insomnia 

in breast cancer survivors, given that almost 

40% of patients experience this symptom,” 

Irwin noted. 

Irwin, who is a Norman Cousins Professor 

for psychoneuroimmunology at UCLA, has 

previously studied TCC in older non-cancer 

patients and found that it not only improved their 

immune functioning, but it also helped lessen 

sleep impairments. “These findings were rather 

unexpected, because we didn’t tell the participants 

that we were looking at sleep effects at all,” he 

recalled. “When we analyzed the data, we found 

out that sleep did, in fact, significantly improve.” 

With NCI funding*, Irwin is now conducting 

a study that compares the effects of TCC with a 

control group of cancer patients who participate 

in a sleep hygiene educational workshop. The 

patients in the TCC group take training classes 

twice weekly for 12 weeks where they learn 20 

separate TCC exercises and movements. They are 

then followed for one year to determine whether 

they maintain their TCC practice and whether it 

improves their sleep. 

Unlike previous TCC studies, “we look at 

objective measures of sleep by doing EEG 

(electroencephalogram) evaluations of sleep 

both before and after the intervention,” Irwin 

explained. “We also are monitoring the levels of 

proinflammatory cytokines. We have found that 

high levels of these biomarkers are associated 

with impairments of sleep.” 

“The importance of this particular behavioral 

intervention is that TCC is so easily accessible for 

individuals, is low cost, and can be administered 

in the community as well as in medical care settings,” Irwin added. “For all those reasons, TCC 

could prove to be a very useful complement in 

treatment of insomnia in patients recovering 

from cancer.” 

Enrollment for the study began early in 2007. 

*Grant number: 1R01CA119159-01A1 

NCI CAM Annual Report 2006 49 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

IMPROVING THE QUALITY OF LIFE FOR CANCER PATIENTS, SURVIVORS, AND THEIR FAMILIES 

Study Will Test the Effect of
 

Tibetan Yoga on Women with Breast Cancer
 

Division of Cancer Control and Population Sciences 

Researchers at The University of Texas M. D. 

Anderson Cancer Center have received a $2.4 

million grant from NCI* to study the effects of 

Tibetan yoga on fatigue and sleep in women with 

breast cancer who are undergoing chemotherapy. 

“Cancer and its treatment are associated with 

considerable distress, impaired quality of life, 

poor mental health, and reduced physical function,” 

explained Principal Investigator Lorenzo Cohen, 

Ph.D., an associate professor in the Departments 

of Behavioral Science and Palliative Care and 

Rehabilitation Medicine. “This is particularly true 

for women with breast cancer who receive multimodality treatment over an extended period of 

time. For thousands of years, Tibetans have been 

employing a form of yoga that we think could 

help ameliorate the treatment-related morbidity 

that accumulates over time in cancer patients.” 

Most of what is known about yoga in the 

West comes from the Indian tradition. For this 

project, Cohen and his colleagues have chosen 

the yoga traditions from Tibet, but they are also 

conducting NCI-funded studies using yogas from 

India (Hatha yoga) and China (Qigong). His team 

was the first to design pilot studies that examined 

the benefits of these techniques in cancer patients. 

They published a 2004 study in the journal Cancer 

that found the practice led to significant sleep 

improvements in patients with lymphoma. 

Another small study of Tibetan yoga also found 

improvements in cancer-related symptoms and 

intrusive thoughts in women with breast cancer. 

Based on those findings, the research team 

will conduct a large randomized trial that 

will compare Tibetan yoga versus simple stretching 

or usual care in women who will be undergoing 

chemotherapy to treat their breast cancer. The 

study’s yoga instructor and co-investigator is 

Alejandro Chaoul, Ph.D., one of few individuals 

in the United States trained in Tibetan yoga. 

“Like other types of yoga, Tibetan yoga involves 

breathing, physical movements, and meditation, 

but it puts greater emphasis on meditation and 

visualization,” he said. The program has been 

closely supervised by the Tibetan yoga master 

Tenzin Wangyal Rinpoche to make sure the 

yoga will be taught as much as possible in the 

original tradition. 

Women with breast cancer who are scheduled to undergo chemotherapy will be randomly 

assigned to either a Tibetan yoga group, a control 

group that does simple stretching exercises, or 

to a group that receives standard care. The participants will practice their assigned techniques 

for seven weeks during chemotherapy and 

then will have five booster sessions over the next 

six months. 

The study will assess the physical and psychological benefits of the yoga program and will 

specifically examine such patient lifestyle factors 

as fatigue and sleep, mental health and distress. 

Additionally, the study will evaluate cognitive and 

emotional processing, social networking and interactions, coping, and other psychosocial factors, 

Cohen said. 

Diana Jeffery, Ph.D., program director, NCI’s 

Office of Cancer Survivorship commented, 

“Approaches like yoga have the potential to help 

women actively participate in breast cancer recovery 

and may increase their sense of control as they 

transition into the post-treatment phase.” 

*Grant number: 1R01CA105023-01A2 

50 NCI CAM Annual Report 2006 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

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 

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 five weeks of weekly hypnotherapy sessions, including training on selfhypnosis, or to a wait-list control group. 

Preliminary findings indicated that women in 

the hypnotherapy group had a 60% reduction in the 

frequency of hot flashes and a 69% 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 and/or 

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.” 

*Grant number: 5R21CA100594-02 

Women in the hypnotherapy group also reported improvements in sleep and mood. 

NCI CAM Annual Report 2006 51 
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, the foundation 

of which occurs 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 

NCI SCIENTISTS SPEARHEAD PIONEERING RESEARCH ON CAM 

NCI Scientists Are Using Mice to Study Selenium
 

and Resveratrol’s Role in Cancer Prevention
 

Center for Cancer Research 

The Center for Cancer Research (CCR) at NCI 

has been a leader in pioneering useful “murine” 

models – the term used to refer to experimental 

studies in mice – which can help predict how 

humans might respond to similar treatments. 

Clinical studies of CAM also benefit from this 

research strategy. This is, in part, due to greater 

control over the animal test subjects, therefore 

making it easier to study diet prevention strategies. 

Large-scale dietary intervention studies in 

humans take many years and are very expensive to 

conduct. Thus, it becomes crucial to learn as much 

as possible in advance about the mechanisms of 

action such dietary components might have, in order 

to refine and focus the subsequent human trials. 

According to Jeffrey E. Green, M.D., head of 

CCR’s Transgenic Oncogenesis Group, “Virtually 

all of our work now focused on preclinical testing 

is in genetically-engineered mouse (GEM) models.” 

During 2006, as in past years, the fruits of NCI 

research on GEMs are made available at no cost 

to cancer researchers in the broader community. 

In the past, mice were often injected with a 

carcinogen, or cancer cells were implanted in mice 

with defective immune systems. Now, researchers 

are able to observe cancers arise and progress in a 

GEM with a fully-functioning endocrine and 

immune system. They are also able to engineer 

mice that are genetically predisposed to develop a 

number of different, specific tumor strains. 

Green has recently been studying the trace 

element selenium, a micronutrient that makes its 

way from the soil into a number of grains and 

vegetables, which can also be used to fortify salt 

and thus delivered to large populations. The CCR 

researchers developed a strain of mouse engineered to develop a specific breast tumor. Mice 

that were engineered with inadequate mechanisms 

for incorporating selenium into proteins had 

more than three times as many breast tumors, he 

reported. Such detailed biological information on 

how dietary components, such as selenium, actually influence carcinogenesis could help to refine 

analysis of large ongoing human trials, such as the 

NCI-sponsored Selenium and Vitamin E Cancer 

Prevention Trial (SELECT). 

“The newest GEM model technologies have 

allowed us to build a better mouse to model 

cancer, no question,” Green noted. “By engineering 

genetic alterations that we know are relevant to 

human cancers, we can now model the onset and 

progression of cancer in a biological milieu that 

is much more like real human disease than any 

previous models.” 

He and other CCR researchers are now actively 

pursuing studies that involve phytochemicals 

found in grape skins.* Resveratrol is a component 

of red grapes that has been shown to inhibit the 

growth of prostate cancer cells. Because the 

mouse models permit such detailed examination 

of the pathways involved, Green wondered if 

other, similar phytochemicals might provide a 

complementary approach to prostate cancer prevention. They are finding that extracts from the 

skins of muscadine grapes contain no resveratrol, 

yet appear to inhibit prostate cancer progression in 

the mice through different mechanisms. 

Such work illustrates the synergy of basic and 

clinical cancer research. “The molecular dissection 

of human cancers continues to identify important 

genes, pathways, and networks that are crucial to 

tumor progression,” explained Green. “Our ability 

to generate new GEM models that reflect that 

refined view of human cancer biology should lead 

to identification of more and better biomarkers of 

cancer development, as well as meaningful 

responses to chemopreventive agents.” 

*Project number: Z01BC005740 

NCI CAM Annual Report 2006 53 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

NCI SCIENTISTS SPEARHEAD PIONEERING RESEARCH ON CAM 

NCI Researcher Investigates How 


Selenium Protects Against Cancer
 

Center for Cancer Research 

Selenium is a trace element found in grains (like 

rice and wheat), meat, seafood, yeast, and certain 

vegetables and plants, especially Brazil nuts. 

Dolph Hatfield, Ph.D., head of the Molecular 

Biology of Selenium section in NCI’s Center 

for Cancer Research (CCR), has been feeding 

selenium to mice for many years. He 

describes selenium as a unique element, “with fascinating properties 

and real opportunities, not only 

as an anticancer agent, but it also 

has the potential to fight viruses, 

delay the aging process, and 

combat heart disease.” 

However, “as a molecular biologist, I must say that we don’t know 

enough about how selenium accomplishes 

these varied health benefits,” cautioned Hatfield. 

There are also some serious divisions in the 

research community over which form of selenium 

works best and whether it might also carry some 

unsuspected risks. 

NIH currently has nearly a dozen clinical trials 

planned or underway in order to develop hard 

evidence about selenium’s protective properties. 

Because their cost will run to hundreds of millions 

of dollars, Hatfield thinks it is crucial to build a 

solid, explanatory, scientific foundation at the 

molecular level. 

“Ironically,” said Hatfield, “it was the 

Nutritional Prevention of Cancer Trial in the mid1990s that illustrated both the promise and the 

perils of selenium.” Researchers were looking for 

a protective effect against recurrent skin cancer 

but instead found that the risk actually increased 

by about 10%. “They got a pleasant surprise when 

they unblinded the study however,” said Hatfield, 

“because it turned out those taking selenium had 

significantly fewer lung, colorectal, and prostate 

cancers” when compared to control subjects. 

Once in the body, selenium makes its way into 

a number of chemically distinct selenoproteins, 

which are manufactured by cells to contain the 

selenium-containing amino acid, selenocysteine. 

Currently, Hatfield’s lab is studying one of those 

selenoproteins thioredoxin reductase 1 (TR1).* 

TR1 is found in abundance in many cancer cells, explained Hatfield, “and we 

think it may actually be driving 

carcinogenesis in a number of 

different cancers, including in 

the liver. Liver cancer is especially 

dangerous, because it presents 

few telltale early symptoms. If we 

could turn down TR1 expression, 

we might be able to prevent it from 

progressing into clinical disease.” 

One of the major NIH trials now underway is 

the Selenium and Vitamin E Cancer Prevention 

Trial (SELECT), which includes more than 

35,000 healthy men over age 55, and the study 

should begin producing results in a few years. 

Meanwhile, Hatfield and his co-workers are 

working hard to clarify which selenoproteins do 

what, in which people, and how these proteins can 

be turned on and off in cancers. 

Hatfield has not been able to rule out the 

possibility that selenomethionine – the seleniumcontaining compound being tested in SELECT – 

may be one of the forms that potentially can also 

have detrimental effects on health. If so, and if 

the men in SELECT who receive selenium have a 

reduced risk of prostate cancer, then information 

will be gained to evaluate the risk-benefit ratio. 

This will allow a better assessment of the appropriateness of evaluating the use of selenomethionine 

for the treatment or prevention of other malignancies. Hatfield is continuing to explore this 

potential toxicity risk. 

*Project number Z01BC005317 

54 NCI CAM Annual Report 2006 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

NCI SCIENTISTS SPEARHEAD PIONEERING RESEARCH ON CAM 

NIH-AARP Diet and Health Study Examines
 

Links Between Nutrition, Weight, and Cancer
 

Division of Cancer Epidemiology and Genetics 

The first published results from the NIH-AARP 

Diet and Health Study* have begun to illuminate 

associations between nutritional and other 

lifestyle factors, including weight gain and exercise, 

and risks for cancer and other diseases. 

The study was developed by investigators 

within the Nutritional Epidemiology Branch of 

DCEG and collaborators from AARP (formerly 

known as the American Association for Retired 

Persons). As the largest in-depth prospective 

cohort study of diet and cancer ever done, the 

NIH-AARP study monitored the health status of 

more than 500,000 AARP members aged 50-71 

from 1995 to 2005 using mailed questionnaires, 

death records, and tumor registry data. The 

numerous analyses of the participants’ health and 

disease status over the ensuing years began to be 

published in 2006 and have already resulted in 

more than 20 articles in major medical journals, 

noted Arthur Schatzkin, M.D., Dr.P.H., DCEG 

Principal Investigator for the NIH-AARP study. 

In the August 24, 2006 issue of the New 

England Journal of Medicine, the research team 

reported that being overweight during midlife is 

linked to an increased risk of death. The analysis of 

nonsmokers at age 50 found that the risk of mortality among participants in the NIH-AARP study 

who were overweight increased by 20% to 40%, 

while mortality risk among obese participants 

increased two to threefold. Excess body weight 

increases the risk of heart disease, stroke, high 

blood pressure, pulmonary disease, and diabetes, 

and is believed to play a role in several cancers. 

Another report, published in early 2007 in the 

journal Cancer, showed that while obese men are 

no more likely to actually develop prostate cancer 

than men of normal weight, they are more likely 

to die from the disease. Additional published 

reports have examined artificial sweetener aspartame and risk for certain cancers, the relationship 

between alcohol consumption and risk of head 

and neck cancer, and the possible role of dietary 

fat in the development of postmenopausal invasive 

breast cancer. 

“I believe this study will be recognized as one 

of the leading studies on nutrition, energy balance, 

and cancer,” Schatzkin noted. “Because of its size, 

the NIH-AARP study provides the opportunity 

to look at the complex interrelationships of dietary 

intake and other factors in development of disease.” 

Future plans include ongoing follow-up of 

the original study participants and expanding the 

study population to include more of the AARP 

membership by using a web-based dietary survey 

instrument. “We are very appreciative of the 

collaboration with AARP – without their members’ 

participation, the study would not have been 

possible,” Schatzkin commented. “The AARP 

leadership has been extremely supportive of the 

study by encouraging participant retention and 

publicizing the study in their publications and 

Web sites.” 

*Project number: Z01 CP01027-11 

Adams KF, Schatzkin A, Harris TB, Kipnis V, Mouw T, BallardBarbash R, Hollenbeck A, Leitzmann MF. Overweight, obesity, and 

mortality in a large prospective cohort of persons 50 to 71 years old. 

N Engl J Med 2006; 355(8):763-778. 

Wright ME, Chang SC, Schatzkin A, Albanes D, Kipnis V, Mouw T, 

Hurwitz P, Hollenbeck A, Leitzmann MF. Prospective study of adiposity and weight change in relation to prostate cancer incidence and 

mortality. Cancer. 2007; 109(4):675-684. 

NCI CAM Annual Report 2006 55 
NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE 

NCI SCIENTISTS SPEARHEAD PIONEERING RESEARCH ON CAM 

Exploring the Role of Cooked 


Red Meat in Cancer Risk
 

Division of Cancer Epidemiology and Genetics 

Not many foods have been shown to be associated with cancer, but by the 1990s, researchers were 

beginning to link the consumption of meat – red 

meat in particular – to some forms of cancer. A 

primary culprit appears to be chemical structures 

known as heterocyclic amines (HCAs), which 

damage cells and have been shown to increase the 

risk of cancer. 

HCAs are not present in uncooked meat but 

can be found abundantly in red meat that is 

cooked at high temperatures for long periods of 

time. They form when amino acids (the building 

blocks of proteins) react with creatine or creatinine 

(a chemical found in muscle) under certain cooking conditions, such as frying and barbecuing. 

Even meat cooked in other ways will form HCAs 

when cooked until “well done.” Also identified 

in some of these studies was a second group of 

carcinogens, polycyclic aromatic hydrocarbons 

(PAHs). 

“A lot of good work in the 1990s in cell and 

animal studies implicated HCAs,” said Rashmi 

Sinha, Ph.D., a senior investigator with NCI’s 

Nutritional Epidemiology Branch within DCEG. 

She was among the first epidemiologic researchers 

who realized that the most meaningful data on the 

link to human cancer would come through large, 

long-term, prospective observational studies. 

Sinha is currently working to develop and refine 

the questionnaires that such studies could use to 

tease out possible cancer links with certain meats 

and how they are prepared.* 

For example, the massive NIH-AARP Diet 

and Health Study included a series of questions 

she and her colleagues developed about meat consumption and preparation in a cohort of more 

than 567,000 men and women between ages 50-69. 

Sinha expects to publish results from responses to 

that study in the near future (see also page 55). 

Another large study – the Prostate, Lung, 

Colorectal and Ovarian (PLCO) Cancer Screening 

Trial – has some 155,000 participants and has 

already begun to confirm some of the associations 

suggested in earlier studies. Sinha was also instrumental in tailoring PLCO food questionnaires to 

shed light on the same issues. 

The estimates that emerged from many of 

the older studies vary, but Sinha believes the new 

epidemiological data that will emerge from these 

large trials will enable researchers to quantify how 

much the increase in cancer risk is attributable to 

high temperature meat preparation. 

*Project number: Z01 CP01027-11 

HCAs are not present in uncooked meat but can be found abundantly in red meat that is cooked at high temperatures 

for long periods of time. 

56 NCI CAM Annual Report 2006 
Scientific Publications
 

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 2006. 

The articles marked with an asterisk are published results of studies features in FY 2005 CAM 

Annual Report. Abstracts of the articles are available online through the National Library of 

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

Cancer Prevention 

* Gail MH, You WC. A factorial trial including 

garlic supplements assesses effect in reducing precancerous gastric lesions. Journal of Nutrition, 

March 2006; 136(3 Suppl): 813S-815S. 

Henning SM, Niu Y, Liu Y, Lee NH, Hara Y, 

Thames GD, Minutti RR, Carpenter CL, Wang H, 

Heber D. Bioavailability and antioxidant effect of 

epigallocatechin gallate administered in purified form 

versus as green tea extract in healthy individuals. 

Journal of Nutritional Biochemistry, October 2005; 

16(10):610-6. 

Hu H, Jiang C, Schuster T, Li GX, Daniel PT, Lu 

J. Inorganic selenium sensitizes prostate cancer cells 

to TRAIL-induced apoptosis through superoxide/ 

p53/Bax-mediated activation of mitochondrial 

pathway. Molecular Cancer Therapeutics, July 2006; 

5(7):1873-82. 

* Huang C, Li J, Song L, Zhang D, Tong Q, Ding 

M, Bowman L, Aziz R, Stoner GD. Black raspberry 

extracts inhibit benzo(a)pyrene diol-epoxideinduced activator protein 1 activation and VEGF 

transcription by targeting the phosphotidylinositol 

3-kinase/Akt pathway. Cancer Research, January 

2006; 66(1):581-7. 

Lam S, McWilliams A, LeRiche J, MacAulay C, 

Wattenberg L, Szabo E. A Phase I study of 

myo-inositol for lung cancer chemoprevention. 

Cancer Epidemiology, Biomarkers & Prevention, 

August 2006; 15(8):1526-31. 

* Lu H, Li J, Zhang D, Stoner GD, Huang C. 

Molecular mechanisms involved in chemoprevention 

of black raspberry extracts: from transcription 

factors to their target genes. Nutrition and Cancer, 

2006; 54(1): 69-78. 

NCI CAM Annual Report 2006 57 
SCIENTIFIC PUBLICATIONS 

Luo H, Tang L, Tang M, Billam M, Huang T, Yu 

J, Wei Z, Liang Y, Wang K, Zhang ZQ, Zhang L, 

Wang JS. Phase IIa chemoprevention trial of 

green tea polyphenols in high-risk individuals of 

liver cancer: modulation of urinary excretion of 

green tea polyphenols and 8-hydroxydeoxyguanosine. 

Carcinogenesis, February 2006; 27(2):262-8. 

Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed 

DN, Mukhtar H. Pomegranate fruit juice for 

chemoprevention and chemotherapy of prostate 

cancer. Proceedings of the National Academy of Sciences, 

October 2005; 102(41):14813-8. 

Mantena SK, Meeran SM, Elmets CA, Katiyar 

SK. Orally administered green tea polyphenols 

prevent ultraviolet radiation-induced skin cancer 

in mice through activation of cytotoxic T cells and 

inhibition of angiogenesis in tumors. Journal of 

Nutrition, December 2005; 135(12):2871-7. 

Reagan-Shaw S, Breur J, Ahmad N. Enhancement 

of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. 

Molecular Cancer Therapeutics, February 2006; 5(2): 

418-29. 

Saleem M, Kweon MH, Johnson JJ, Adhami VM, 

Elcheva I, Khan N, Bin Hafeez B, Bhat KM, 

Sarfaraz S, Reagan-Shaw S, Spiegelman VS, 

Setaluri V, Mukhtar H. S100A4 accelerates 

tumorigenesis and invasion of human prostate 

cancer through the transcriptional regulation of 

matrix metalloproteinase 9. Proceedings of the National 

Academy of Sciences, October 2006; 103(40):14825-30. 

Shukla S, Mishra A, Fu P, MacLennan GT, 

Resnick MI, Gupta S. Up-regulation of insulinlike growth factor binding protein-3 by apigenin 

leads to growth inhibition and apoptosis of 

22Rv1 xenograft in athymic nude mice. FASEB 

Journal, December 2005; 19(14):2042-2044. 

Siddiqui IA, Zaman N, Aziz MH, Reagan-Shaw 

SR, Sarfaraz S, Adhami VM, Ahmad N, Raisuddin 

S, Mukhtar H. Inhibition of CWR22Rnu1 tumor 

growth and PSA secretion in athymic nude mice 

by green and black teas. 1: Carcinogenesis, April 

2006; 27(4):833-9. 

Yun JM, Kweon MH, Kwon H, Hwang JK, 

Mukhtar H. Induction of apoptosis and cell cycle 

arrest by a chalcone panduratin A isolated from 

Kaempferia pandurata in androgen-independent 

human prostate cancer cells PC3 and DU145. 1: 

Carcinogenesis, July 2006; 27(7):1454-64. 

Cancer Treatment 

* Chen X, Murakami T, Oppenheim JJ, Howard 

OM. Triptolide, a constituent of immunosuppressive 

Chinese herbal medicine, is a potent suppressor of 

dendritic-cell maturation and trafficking. Blood, 

October 2005; 106(7): 2409-16. 

Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar 

H. Targeting multiple signaling pathways by green 

tea polyphenol (-)-epigallocatechin-3-gallate. 

Cancer Research, March 2006; 66(5):2500-5. 

Kijima I, Phung S, Hur G, Kwok SL, Chen S. 

Grape seed extract is an aromatase inhibitor and a 

suppressor of aromatase expression. Cancer Research, 

June 2006; 66(11):5960-7. 

58 NCI CAM Annual Report 2006 
SCIENTIFIC PUBLICATIONS 

Saleem M, Kaur S, Kweon MH, Adhami VM, 

Afaq F, Mukhtar H. Lupeol, a fruit and vegetable 

based triterpene, induces apoptotic death of human 

pancreatic adenocarcinoma cells via inhibition of 

Ras signaling pathway. Carcinogenesis, November 

2005; 26(11):1956-64. 

Saleem M, Kweon MH, Yun JM, Adhami VM, 

Khan N, Syed DN, Mukhtar H. A novel dietary 

triterpene Lupeol induces fas-mediated apoptotic 

death of androgen-sensitive prostate cancer cells 

and inhibits tumor growth in a xenograft model. 

Cancer Research, December 2005; 65(23):11203-13. 

Singh SV, Zeng Y, Xiao D, Vogel VG, Nelson JB, 

Dhir R, Tripathi YB. Caspase-dependent apoptosis 

induction by guggulsterone, a constituent of 

Ayurvedic medicinal plant Commiphora mukul, 

in PC-3 human prostate cancer cells is mediated 

by Bax and Bak. Molecular Cancer Therapeutics, 

November 2005; 4(11):1747-54. 

Veluri R, Singh RP, Liu Z, Thompson JA, Agarwal 

R, Agarwal C. Fractionation of grape seed extract 

and identification of gallic acid as one of the 

major active constituents causing growth inhibition 

and apoptotic death of DU145 human prostate 

carcinoma cells. Carcinogenesis, July 2006; 27(7): 

1445-53. 

Yamaguchi K, Liggett JL, Kim NC, Baek SJ. Antiproliferative effect of horehound leaf and wild 

cherry bark extracts on human colorectal cancer 

cells. Oncology Reports, January 2006; 15(1):275-81. 

Cancer Side Effects / Symptom 

Management 

Ezzo J, Vickers A, Richardson MA, Allen C, 

Dibble SL, Issell B, Lao L, Pearl M, Ramirez G, 

Roscoe JA, Shen J, Shivnan J, Streitberger K, 

Treish I, Zhang G. Acupuncture-point stimulation 

for chemotherapy-induced nausea and vomiting. 

Journal of Clinical Oncology, October 2005; 23(28): 

7188-98. 

Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow 

G, Pentland A, Ryan JL, Ding I. Curcumin protects against radiation-induced acute and chronic 

cutaneous toxicity in mice and decreases mRNA 

expression of inflammatory and fibrogenic 

cytokines. International Journal of Radiation Oncology, 

Biology, Physics, July 2006; 65(3):890-8. 

Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, 

Barton DL, Sloan JA, Lavasseur BI, Rao RM, 

Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, 

Richelson E, Fauq AH. Phase III double-blind, 

randomized, placebo-controlled crossover trial of 

black cohosh in the management of hot flashes: 

NCCTG Trial N01CC1. Journal of Clinical Oncology, 

June 2006; 24(18):2836-41. 

NCI CAM Annual Report 2006 59 
Appendix 

An NCI-sponsored clinical trail 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 Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Pediatric Trials 

Randomized Study of Electroacupuncture 

for Treatment of Delayed ChemotherapyInduced 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 Prospective Pilot Study of 

Acupressure in Preventing ChemotherapyAssociated Nausea and Vomiting in 

Pediatric Patients With Cancer 

CCCWFU-02104 Supportive care 2 to 21 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 

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 

Phase I Study of Beta-Glucan and 

Rituximab in Pediatric Patients With 

Relapsed or Progressive CD20-Positive 

Lymphoma or Leukemia or PostAllogeneic Stem Cell Transplant-Related 

Lymphoproliferative Disorder 

MSKCC-03095 Treatment Under 22 NCI Phase I 

60 NCI CAM Annual Report 2006 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

Randomized Study of the Molecular 

Effects of Lycopene Versus Omega-3 

Fatty Acid Nutritional Supplements in 

Patients With Stage I or II Prostate Cancer 

UCSF-03553 Biomarker/Laboratory 

analysis; Treatment 

Not specified NCI No phase specified 

Phase II Randomized Study of 

Neoadjuvant Genistein in Patients 

Undergoing Surgical Resection for 

Bladder Cancer 

WCCC-CO-04307 Biomarker/Laboratory 

analysis; Treatment 

18 and over NCI Phase II 

Chemoprevention 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-CPC-04131-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 Lycopene as 

Chemoprevention for Prostate Cancer 

in Healthy Participants 

UIC-2004-0217 Prevention; Biomarker/ 

Laboratory analysis 

18 and over NCI No phase specified 

Phase I Study of Lycopene as 

Chemoprevention for Prostate Cancer 

in Healthy Participants 

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

Phase I Randomized Study of FolateDepleted 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 Randomized Chemoprevention 

Study of Indole-3-carbinol in Healthy 

Participants 

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

NCI CAM Annual Report 2006 61 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

Phase I Pilot Chemoprevention Study CHNMC-IRB-03178 

of IH636 Grape Seed Proanthocyanidin 

Extract in Healthy Postmenopausal Women 

at High Risk of Developing Breast Cancer 

Prevention 40 to 75 NCI Phase I 

Phase I Randomized Study of 

Bowman Birk Inhibitor Concentrate 

in Healthy Male Participants 

UPCC-706366 Prevention 18 to 65 NCI Phase I 

Phase IB Randomized Study of 

Green Tea Extract (Polyphenon E) in 

Preventing Esophageal Cancer in Patients 

With Barrett’s Esophagus 

MDA-03101 Prevention 18 and over 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 HighGrade Prostatic Intraepithelial Neoplasia 

CINJ-080404 Prevention 18 and over NCI Phase II 

Phase II Randomized Study of Green Tea 

Extract (Polyphenon E) for the Prevention 

of Cervical Cancer in Patients With 

Human Papillomavirus (HPV) and 

Low-Grade Cervical Intraepithelial 

Neoplasia (CIN 1) 

UARIZ-UAZ03-1-02 Prevention 18 and over NCI Phase II 

Phase II Randomized Study of Genistein 

in Women at High Risk For Breast Cancer 

NU-NWU03-1-04 Prevention 25 and older 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 II Randomized Chemoprevention MAYO-030103 

Study of Atorvastatin Versus OligofructoseEnriched Inulin (Raftilose Synergy 1) 

Versus Sulindac in Patients at Increased 

Risk of Developing Sporadic Colorectal 

Neoplasia 

Prevention; Biomarker/ 

Laboratory analysis 

40 and over NCI Phase II 

Phase II Chemoprevention Study of 

Curcumin in Current Smokers With 

Aberrant Crypt Foci 

UCIRVINE-UCI04-2-01 Prevention; Biomarker/ 

Laboratory analysis 

40 and over 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 

62 NCI CAM Annual Report 2006 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

Phase III Randomized Study of 

Selenium in Patients With Adenomatous 

Colorectal Polyps 

UARIZ-HSC-00142 Prevention 40 to 80 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 

Randomized Pilot Study of Glutamine 

Supplementation for the Prevention of 

Paclitaxel-Induced Myalgia and/or 

Arthralgia in Patients With Cancer 

OHSU-ONC-99037-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-2003P-000299 Supportive care 18 and over NCI No phase specified 

Randomized Study of Coenzyme Q10 

to Relieve Treatment-Related Fatigue in 

Women With Breast Cancer 

CCCWFU-97202 Supportive care Any age NCI No phase specified 

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 

Randomized Study of American Ginseng 

in Patients With Cancer-Related Fatigue 

NCCTG-N03CA Supportive care 18 and over NCI No phase specified 

Pilot Study of Healing Touch in Treating 

Patients Receiving Chemotherapy For 

Acute Myeloid Leukemia or Acute 

Lymphocytic Leukemia 

CCCWFU-02305 Supportive care 18 and over NCI No phase specified 

Randomized Pilot Study of Hypnosis in 

Controlling Hot Flashes in Women Who 

are Breast Cancer Survivors 

S-WHITE-8165 Supportive care Over 18 NCI No phase specified 

Pilot Study of a Stress Reduction Program 

in Patients With Malignant Brain Tumors 

and Their Family Caregivers 

CASE-CCF-2306-CC052 Supportive care 18 and over NCI No phase specified 

NCI CAM Annual Report 2006 63 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

Randomized Study of Music in Reducing CCCWFU-98306 

Anxiety and Perceived Pain in Adult Patients 

Who Are Undergoing Bone Marrow Biopsy 

for Hematologic Cancers or Other Diseases 

Supportive care 18 and over 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; 21 and over 

Educational/Counseling/ 

Training; Behavioral 

study 

NCI No phase specified 

Pilot Study of Restorative Yoga for CCCWFU-02403 

Symptom Management and Stress Reduction 

in Women With Ovarian or Breast Cancer 

Supportive Care: 18 and over 

Educational/Counseling/ 

Training 

NCI No phase specified 

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 

Educational/Counseling/ 

Training 

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 

Educational/Counseling/ 

Training 

NCI No phase specified 

Phase II Randomized Study of Soy Protein CALGB-79805 

in Postmenopausal Women With Breast 

Disease Taking Tamoxifen and Experiencing 

Hot Flashes 

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 ChemotherapyInduced Nausea and Vomiting 

CCUM-0201 Supportive care 18 and over NCI; NCCAM Phase II 

Phase II Study of Hypericum Perforatum 

(St. John's wort) in Postmenopausal Women 

With Non-Metastatic Breast Cancer 

Suffering From Hot Flashes 

CCCWFU-98301 Supportive care 18 and over 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 

64 NCI CAM Annual Report 2006 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

Phase III Randomized Study of MSKCC-03131A 

Acupuncture Versus Standard of Care 

in Treating Pain and Dysfunction in Patients 

With Head and Neck Cancer Who Have 

Undergone Neck Dissection 

Supportive care Not specified NCI Phase III 

Phase III Randomized Study of (Valerian) NCCTG-N01C5 

for Improving Sleep in Patients With Cancer 

Receiving Adjuvant Therapy 

Supportive care 18 and over NCI Phase III 

Phase III Randomized Study of Creatine in NCCTG-N02C4 

Patients With Cancer-Associated Weight Loss 

Supportive care 18 and over NCI Phase III 

Phase III Randomized Study of ECOG-E4Z02 

Levocarnitine (L-carnitine) for the 

Management of Fatigue in Cancer Patients 

Supportive care 18 and over NCI Phase III 

Phase III Randomized Study of Alpha­ MDA-CCC-0327 

Lipoic Acid in Preventing Platinum-Induced 

Peripheral Neuropathy in Cancer Patients 

Receiving a Cisplatin- or OxaliplatinContaining Chemotherapy Regimen 

Supportive care Not specified NCI Phase III 

Pilot Study to Evaluate the Influence of NCI-04-C-0084 

Garlic on the Pharmacokinetics of 

Docetaxel in Patients With Locally 

Advanced or Metastatic Breast Cancer 

Treatment 18 and over NCI No phase specified 

Randomized Study of Pomegranate Juice UCLA-0507059-01 

in Patients With Rising Prostate-Specific 

Antigen Levels After Surgery or 

Radiotherapy for Localized Prostate Cancer 

Treatment 18 and over NCI; No phase specified 

Pharmaceutical/ 

Industry 

Randomized Pilot Study of Isoflavones MCC-0105 

Versus Lycopene Prior to Radical 

Prostatectomy in Patients With Localized 

Prostate Cancer 

Treatment; Biomarker/ 45 to 80 NCI No phase specified 

Laboratory analysis 

Phase I Study of Gemcitabine and Mistletoe NCCAM-02-AT-260 

in Patients With Advanced Solid Tumors 

Treatment 18 and over NCCAM: Phase I 

NCI; Other 

Phase I Study of Calcitriol and Gefitinib RPCI-RPC-0207 

With or Without Dexamethasone in 

Patients With Advanced Solid Tumors 

Treatment 18 and over NCI; Phase I 

Pharmaceutical/ 

Industry 

Phase I Study of Nordihydroguaiaretic UCSF-035510 

Acid in Patients With Nonmetastatic, 

Biochemically Relapsed Prostate Cancer 

Treatment Over 18 NCI Phase I 

Phase I Study of Absorption-Enhanced WSU-D-2979 

Diindolylmethane (BioResponse-DIM) in 

Patients With Nonmetastatic, HormoneRefractory Prostate Cancer and Rising 

Prostate-Specific Antigen Levels 

Treatment 18 and over NCI Phase I 

NCI CAM Annual Report 2006 65 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

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 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 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 Fat- and/or Flaxseed-Modified Diets 

in Patients With Newly Diagnosed 

Prostate Cancer 

DUMC-1385-02-7R3ER 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 

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 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 Pilot Study of Genistein and 

High-Dose Interleukin-2 in Patients With 

Metastatic Malignant Melanoma or Renal 

Clear Cell Carcinoma 

NU-04V1 Treatment 18 and over NCI; 

Pharmaceutical/ 

Industry 

Phase II 

66 NCI CAM Annual Report 2006 
APPENDIX 

PDQ Clinical Trials Primary ID Type of Trial Age Range Sponsor of Trial Phase(s) 

Adult Trials 

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 

Platinum-Based 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 NCI; NCCAM Phase III 

NCI CAM Annual Report 2006 67 
Organizational Chart 

In FY 2006, OCCAM was one of 16 offices within NCI’s Office of the Director. 

Office of the Director Special Assistant for Program Coordination 

Office of Management NCI-Frederick 

Center to Reduce Cancer Health Disparities Office of Communications 

Office of Centers, Training and Resources Office of Policy, Analysis & Response 

Coordinating Center for Clinical Trials Ethics Office 

Office of International Affairs Office of Budget and Financial Management 

Office of Education and Special Initiatives Office of Cancer Complementary and Alternative Medicine 

Center for Advanced Technologies and Strategic Partnerships Center for Bioinformatics 

Office of Science Planning and Assessment Office of Workforce Development 

68 NCI CAM Annual Report 2006 

NIH Publication No. 07-6117
 

Printed February 2008