office of cancer complementary and 

alternative medicine

annual report on

Complementary

and Alternative

Medicine

fiscal year

2011

i

nci’s annual report on complementary and alternative medicine: fiscal year 2011

Director’s Message

The research the National Cancer Institute (NCI) supports, both in its own laboratories and at institutions 

worldwide, is focused on the ultimate goal of helping cancer patients. That mission – achieved through rigorous 

science – extends to NCI’s program on complementary and alternative medicine, also known as CAM. It is with 

great pleasure and pride that we once again provide NCI’s research partners, physicians, the advocacy community, 

policymakers, and cancer patients with this seventh annual review of NCI’s extensive accomplishments in advancing 

evidence-based CAM interventions and therapies. 

This report includes information about an extensive and diverse portfolio of research with projects ranging from the 

use of food-derived substances, diet modification and exercise for cancer prevention or treatment, to studies of the 

use of acupuncture to diminish side effects of standard cancer therapy. 

NCI’s commitment to CAM research and evidence-based clinical practice has been steadily supported, coordinated, 

and expanded by the Office of Cancer Complementary and Alternative Medicine (OCCAM) over the years. 

OCCAM’s goal is to increase NCI’s ability to extend the search for effective therapies into areas that show promise 

but which often are not thoroughly explored in conventional biomedical research.

I hope you find this report helpful and informative. I also hope that it will generate an enhanced dialogue – 

especially between patients and health care professionals – about the appropriate uses of CAM interventions 

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 and support the science that 

makes wise and informed decisions possible.

Jeffrey D. White, M.D.

Director

Office of Cancer Complementary and Alternative Medicine

Division of Cancer Treatment and Diagnosis

National Cancer Institute
ii

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011

FIGURE 1: MAJOR CATEGORIES OF CAM THERAPIES

alternative medical systems 

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: Ayurveda, Homeopathy, Traditional 

Chinese Medicine, Tibetan Medicine

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

exercise therapies

definition: Exercise therapies include health-enhancing systems of exercise 

and movement.

examples: T’ai chi, Yoga asanas

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

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, Imagery, Relaxation therapy, 

Music therapy, Cognitive-behavioral therapy, 

Aromatherapy

nutritional therapeutics 

definition: Nutritional therapeutics are an assortment of nutrients and nonnutrients, bioactive food components used as chemo-preventive agents, and 

specific foods or diets used as cancer prevention or treatment strategies.

examples: Macrobiotic diet, Vegetarianism, 

Gerson therapy, Kelley/Gonzalez regimen, 

Vitamins, Soy 

pharmacological and biologic treatments 

definition: Pharmacological and biologic treatments include the off-label use 

of certain prescription drugs, hormones, complex natural products, vaccines, 

and other biological interventions not yet accepted in mainstream medicine. 

examples: Antineoplastons, Low-dose 

naltrexone, Immunoaugmentative therapy, 

Laetrile 

sub-category: Complex Natural Products 

definition: Complex natural products are 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, 

Mistletoe, Mixtures of tea polyphenols

spiritual therapies 

definition: Spiritual therapies are therapies that focus on deep, often 

religious beliefs and feelings, including a person’s sense of peace, purpose, 

connection to others, and beliefs about the meaning of life.

examples: Intercessory prayer, Spiritual healing
iii

Contents

Director’s Message .......................................................................... i

Figure 1: Major Categories of CAM Therapies ................................................. ii

Introduction .............................................................................. 1

CAM RESEARCH PORTFOLIO ANALYSIS FY2011 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

The CAM Portfolio Analysis Process ...................................................... 3

OFFICE OF CANCER COMPLEMENTARY AND ALTERNATIVE MEDICINE (OCCAM) . . . 7

OCCAM Programs .................................................................... 8

NCI RESEARCH IN COMPLEMENTARY AND ALTERNATIVE MEDICINE

HIGHLIGHTS FROM NCI’S CAM TRAINING PROJECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Testing Vegetable Compounds to Boost Breast Cancer Survival .............................. 12

Tomato and Soy Combination Studied for Prostate Cancer Prevention ......................... 13

HIGHLIGHTS FROM NCI’S CAM RESEARCH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

Coffee Drinking Not Unhealthy and is Possibly Associated with Lower Risk of Death ........... 15

Researcher Investigates a Vitamin’s Potential Dual Effect on Cancer .......................... 16

Evidence Emerges for the Health Risks of Sedentary Behavior ............................... 17

ACCELERATING PROGRESS IN CANCER PREVENTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Finding a Healthy Dietary Ratio for Prostate Cancer Prevention .............................. 20

Complementary Strategies for Prostate Cancer Prevention and Management ................... 21

Plant-Based Chemoprevention Investigated for Lung Cancer ................................. 22

DEVELOPING EFFECTIVE AND EFFICIENT TREATMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Antioxidant Enzymes Show Unexpected Behavior in Leukemia Cells Treated 

with Imatinib ......................................................................... 24

High-Fat Diet May Enhance Cancer Patients’ Response to Treatments ........................ 25

Soy Used to Protect Normal Cells While Sensitizing Cancer Cells to Radiation ................. 27

IMPROVING THE QUALITY OF LIFE FOR CANCER PATIENTS, SURVIVORS, 

AND THEIR FAMILIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Impact of Exercise on Ovarian Cancer Prognosis Studied ................................... 29

Acupuncture Studied to Prevent Radiation-Induced Chronic Dry Mouth ...................... 31

Exercise Study for Metastatic Breast Cancer Patients May Offer Benefits ....................... 32

APPENDIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
iv
1

Introduction

This report highlights the National Cancer Institute’s initiatives and annual expenditures in complementary and 

alternative medicine (CAM)* research. It is intended as a way for NCI to communicate its progress in this area 

of medical research to all interested stakeholders including cancer researchers, CAM practitioners, health care 

providers, advocacy organizations, cancer patients, and the general public.

This publication provides an overview of the NCI-supported work in this field along with details on selected cancer 

CAM research projects. For more information on specific projects included in this report, please visit the NIH 

Research Portfolio Online Reporting Tools (RePORTER) database and search the grant or project number.

This report highlights projects, grants, and cooperative agreements supported by each of the Institute’s extramural 

grant funding divisions – the Division of Cancer Biology (DCB), the Division of Cancer Control and Population 

Sciences (DCCPS), the Division of Cancer Prevention (DCP), and the Division of Cancer Treatment and Diagnosis 

(DCTD), along with projects from NCI’s intramural laboratories in the Center for Cancer Research (CCR) and 

the 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 2011, NCI’s research expenditures for CAM are an estimated $105,341,737 for the funding of 382 CAM 

research projects. As this report on cancer CAM indicates, we at the NCI are committed to an integrated approach to 

bring together all of the many resources and approaches necessary to decrease the frequency, destructiveness, and 

lethality of cancer. We believe that evidence-based CAM techniques, systems, and products can have an important 

role in reaching 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 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 ii for the major categories of CAM therapies.)
cam research 

portfolio analysis

fy 2011

2
3

c a m r ese a rch port fol io a na lysis f y2011

The CAM Portfolio Analysis Process

How much money does NCI spend on CAM research each year? 

This is one of the questions most frequently posed to OCCAM. 

Researchers, cancer patient advocates, proponents of CAM, 

and Congress are interested in the answer, and OCCAM is 

responsible for gathering the data needed to report the total CAM 

expenditures budget figure each year. 

It is a common misconception that OCCAM manages all of 

the CAM projects for NCI. The vast majority of CAM projects 

are managed by other programs and laboratories throughout 

the Institute. After the close of the fiscal year, NCI’s Division 

of Extramural Activities (DEA) provides OCCAM with a list of 

funded grants and cooperative agreements coded as containing 

some component of CAM research. Similarly, NCI’s two 

intramural components, the Center for Cancer Research (CCR) 

and the Division of Cancer Epidemiology and Genetics (DCEG), 

provide lists of their potentially relevant projects. Also, a 

list of contracts identified as potentially containing CAM 

research is provided. OCCAM staff review each project to 

confirm they are accurately classified as CAM research. Then, 

aspects of each project are identified allowing their placement 

into sub-categories based on the type of research and CAM 

intervention investigated. 

NCI’s total CAM expenditure figure includes money awarded 

for intramural projects (projects conducted within NIH facilities 

and labs), extramural grants (projects conducted outside of 

NIH), cooperative agreements, contracts, and supplements. 

It is important to note the reported figure for total NCI CAM 

expenditures for a fiscal year only includes projects for which 

NCI is the primary funder.

FY 2011:

$105,341,737

INVESTED IN 

CAM RESEARCH

Nutritional 

Therapeutics

Pharmacological 

and 

Biologic 

Treatments

Exercise 

Therapies

Mind-Body 

Interventions

Alternative 

Medical 

Systems

Manipulative 

and 

Body-based 

Methods

Spiritual 

Therapies

Energy 

Therapies

NCI’s total CAM expenditure figure includes money awarded for intramural 

projects, extramural grants, cooperative agreements, contracts, and supplements
4

total estimated cancer cam 

research expenditure

In FY 2011, NCI invested $105,341,737 for 382 intramural and 

extramural research projects relevant to CAM. For the purpose 

of the FY 2011 analysis, the following types of funding are 

included: intramural projects and extramural grants, cooperative 

agreements, contracts, and supplements (Figure 2). 

The above numbers do not include CAM training grants 

(T and F awards), K (research career) or R25 (cancer education) 

grants. These numbers are listed separately in 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 2011, 60.8% 

of cancer CAM-related research project funds went to various 

cancer prevention efforts, while treatment, symptom/side effects 

management, epidemiology, and conferences received 18.4%, 

15.2%, 5.5%, and 0.03% respectively.

FIGURE 2: NCI CAM EXPENDITURES FY 2003–2011*

$119,900,000

$128,671,113

$121,076,919

$123,076,167

$121,932,765 $121,264,507

$114,441,501 $114,460,116

$105,341,737

$100

$105

$110

$115

$120

$125

$130

$135

2003 2004 2005 2006 2007 2008 2009 2010 2011

MILLIONS

* Includes grants, cooperative agreements, intramural projects, and contracts. Grants and cooperative agreements are only included when NCI is the primary funding agency. 

Excludes training grants (T’s, F’s, K’s and R25s). Total projects include all active projects in FY2011.

FIGURE 3: NCI CAM TRAINING PROJECTS 2011 

Training Grant Mechanisms Number of Grants Total Funding

F (31,32) 4 $132,157

K (01, 05, 07, 22, 23, 24) 16 $1,434,554

R25 4 $760,861

T32 3 $472,829

TOTAL 27 $2,800,401

FIGURE 4: NCI CAM RESEARCH PROJECTS BY RESEARCH TYPE*

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

agreements are only included when NCI is the primary funding agency. Excludes training grants (T’s, F’s, K’s 

and R25s). Total projects include all active projects in FY2011.

Prevention

$64,027,446

60.8%

Treatment

$19,393,078

18.4%

Symptom/Side-Effect 

Management

$16,044,970

15.2%

Epidemiology

$5,845,984

5.5%

Conferences

$30,260

0.03%
5

breakdown by major cam therapy category

In FY 2011, NCI performed or supported research addressing a 

variety of CAM approaches (Figure 5). These CAM therapies fall 

into nine groups: alternative medicine systems, energy therapies, 

exercise therapies, manipulative and body-based methods, mindbody interventions, nutritional therapeutics, pharmacological and 

biologic treatments, spiritual therapies, and miscellaneous. 

The largest percentage (70.1%) of CAM research funding went to 

projects that investigated nutritional therapeutics, which can 

be further broken out into subcategories of research on: foods 

(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); fats (e.g., linoleic 

acid and omega-3); and amino acids and proteins (e.g., N-acetyl 

cysteine and glycine). 

Figure 6 shows the distribution of projects by the subcategories of 

nutritional therapeutics.

FIGURE 5: NCI CAM RESEARCH PROJECTS BY CAM CATEGORY*

A

Nutritional 

Therapeutics

B

Pharmacological and 

Biologic 

Treatments

C

Exercise 

Therapies

D

Mind-Body 

Interventions

E

Miscellaneous

F

Alternative 

Medical 

Systems

G

Energy 

Therapies

H

Manipulative 

and 

Body-based 

Methods

I

Spiritual 

Therapies

$73,822,107

70.1%

$11,241,945

10.7%

$7,952,892

7.6%

$4,554,383

4.3%

$3,002,474

2.9%

$2,259,428

2.1%

$1,195,143

1.1%

$755,576

0.7%

$557,790

0.5%

FIGURE 6: NCI CAM NUTRITIONAL THERAPEUTICS 

PROJECTS BY CATEGORY*

Bioactive Food 

Components

$31,714,657

43%

Vitamins

$15,042,720

20.4%

Minerals

$10,938,499

14.8%

Fats

$6,322,891

8.6%

Dietary Regimens

$6,150,586

8.3%

Food

$3,437,537

4.7%

Amino Acids and Proteins

$215,217

0.3%

c a m r ese a rch port fol io a na lysis f y2011

* Includes grants, cooperative agreements, intramural projects, and contracts. Grants and cooperative agreements are only included when NCI is the primary funding agency. Excludes training grants (T’s, F’s, K’s and R25s). 

Total projects include all active projects in FY2011.
6

breakdown by cancer type

The research projects that make up NCI’s FY 2011 CAM research 

portfolio address 19 categories of cancer types. Among the 

various categories, prostate, breast, colorectal, and lung cancers 

received the largest amounts of cancer CAM research funding. 

Nearly 25% of NCI’s cancer CAM research funding supported 

projects addressing “multiple types” of cancer. 

For a complete listing of the cancer type categories and estimated 

funding amounts, please see Figure 7 below.

FIGURE 7: NCI CAM RESEARCH PROJECTS BY CANCER TYPE*

Bladder $1,821,067

Brain $503,280

Breast $17,906,361

Cervical $606,829

Childhood Cancer $480,646

Colorectal $18,868,169

Esophageal $1,198,777

Gastric $2,012,671

Head and Neck $3,147,427

Hematologic $2,089,455

Kidney $41,578

Liver $1,015,442

Lung $5,980,610

Various (Multiple Types) $25,898,621

Ovarian $835,888

Pancreatic $3,485,480

Prostate $15,694,395

Skin: Non-Melanoma and Melanoma $3,422,254

Thyroid $332,786

Total $105,341,737

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

agreements are only included when NCI is the primary funding agency. Excludes training grants (T’s, F’s, K’s 

and R25s). Total projects include all active projects in FY2011.

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
7

office of cancer 

complementary 

and alternative 

medicine (occam)
8

NCI’s Office of Cancer Complementary and Alternative 

Medicine (OCCAM) is a coordinating office responsible for: 

identifying gaps in the science and creating corresponding 

funding opportunities for cancer CAM research; partnering 

with NCI program staff and other governmental and 

nongovernmental organizations to increase the testing of 

CAM approaches for cancer prevention, diagnosis, treatment, 

symptom management, and rehabilitation; developing 

communication products for various audiences concerning 

the investigation and use of these approaches; and helping 

to build bridges between CAM practitioners and the cancer 

research community.

OCCAM is part of the NCI Division of Cancer Treatment and 

Diagnosis (DCTD). The division’s mission is to improve the 

lives of the American public by discovering and conducting 

better ways to diagnose, assess, treat, and cure cancer through 

stimulating, coordinating, and funding a national program of 

cancer research. OCCAM’s programs and activities complement 

DCTD’s mission and are enhanced by the other major programs 

and branches within DCTD.

OCCAM‘s research priorities include: 

•	 Identifying novel therapeutics in the pharmacopeia 

of traditional medical systems as defined by the World 

Health Organization 

•	 Research of complementary approaches to improve 

the therapeutic ratio of standard and investigational 

anti-cancer therapies

•	 Research on lifestyle modifications (e.g., diet, exercise, mindbody approaches) for their impact on cancer outcomes such 

as response to conventional cancer therapy and survival

OCCAM Programs 

extramural research program

OCCAM’s Extramural Research Program (ERP) staff manages 

a portion of NCI’s CAM research portfolio, works with other 

program staff throughout NCI on CAM research issues, assists 

investigators in identifying funding opportunities, and provides 

guidance to applicants in the pre- and post- review periods of 

grant applications. The staff also coordinates programs and 

initiatives designed to stimulate research in cancer CAM as well 

as activities to develop the foundation of the science in cancer 

CAM research.

ERP continued to support funding opportunity announcements 

(FOAs) for developmental and small grant mechanisms R21 

and R03, entitled “Developmental Projects in Complementary 

Approaches to Cancer Care and Treatment” for part of FY11. 

The R21 funding opportunities encouraged and supported the 

development of basic and clinical complementary and alternative 

cancer research projects (prevention, therapeutic, and palliative) 

through exploratory/developmental research grants. The R03 

mechanism offered researchers a chance to generate data 

needed for conducting larger scientific studies of CAM. OCCAM 

continues to encourage new and young as well as veteran 

investigators to pursue research in areas not typically explored in 

studies funded by larger grant mechanisms. R21 and R03 grants 

provide that opportunity. 

In FY11, NCI continued co-sponsoring three program 

announcements which specifically solicited CAM-related 

research:

•	 Biology of Manual Therapies (R01) PA-10-209

(Expires 1/8/2014)

•	 Biology of Manual Therapies (R21) PA-10-210

(Expires 1/8/2014)

•	 Limited Competition: Fogarty International Research 

Collaboration – Basic Biomedical (FIRCA-BB) Research 

Award (R03) PAR-11-037 (Expired 1/11/2012)

Highlights from OCCAM’s Grant Portfolio

In FY 2011, NCI, along with the National Center for 

Complementary and Alternative Medicine (NCCAM) and the 

NIH Office of the Director, funded a P01 project grant* to 

investigate the effectiveness of PHY906 as a modulator of the 

chemotherapy drug irinotecan in the treatment of patients 

with metastatic colorectal cancer. PHY906 is an extract of four 

herbs based on a formula of traditional Chinese medicine 

(TCM), known as Huang Qin Tang (HQT). HQT is used as a 

treatment for gastrointestinal ailments, including diarrhea, 

nausea, and vomiting. Preclinical data suggests PHY906 can 

help improve the gastrointestinal side effects of irinotecan while 

simultaneously increasing the drug’s anticancer activity.

The study, titled “Chinese Herbal Medicine as a Novel Paradigm 

for Cancer Chemotherapy,” is led by Principal Investigator 

Yung-chi (Tommy) Cheng, Ph.D., of Yale University. The study 

has three main goals: 1) to confirm in humans that combining 

PHY906 with irinotecan may result in greater cancer-cell killing 

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
9

office of c a ncer compl emen ta ry a nd a lt er nat i v e medicine

abilities of the chemotherapy drug, improve treatment side 

effects, and increase quality of life for the patients; (2) to explore 

the potential mechanisms of action of PHY906 by identifying 

specific molecular factors of the herbal mixture and their byproducts; and (3) to develop novel and appropriate statistical and 

computational modeling methods for use in analyzing data from 

clinical effectiveness studies of herbal extracts. 

It is the hope of the scientists that this study may generate 

new methods for developing herbal or botanical medicines in 

combination with conventional chemotherapy for the treatment 

of cancer.

Further information on this project is available online, 

http://projectreporter.nih.gov/project_info_description.

cfm?aid=8175586&icde=0.

*Project number: 1P01CA154295-01A1

OCCAM Grant Portfolio

OCCAM managed several grants in FY 2011. Additional 

information about each grant can be obtained by searching the 

project number in the NIH RePORTER database. 

OCCAM Newly Funded Grants in FY 2011

•	 R21CA161182, Using Ketogenic Diets to Enhance 

Radio-Chemo-Therapy Response: A Phase I Trial, 

Project End 8/31/2013 

•	 R21CA155518, Soy Isoflavones to Augment Radiotherapy 

of Lung Carcinoma, Project End 8/31/2013

•	 P01CA154295, Chinese Herbal Medicine as a Novel 

Paradigm for Cancer Chemotherapy, Project End 8/31/2016

case review and intramural 

science program

The mission of the Case Review and Intramural Science 

Program (CRISP) is to identify novel complementary and 

alternative (CAM) therapies for the treatment of cancer. This aim 

is accomplished through various program activities, such as the 

rigorous scientific evaluation of retrospective case reports (NCI 

Best Case Series Program) and round table discussions with 

cancer experts and CAM practitioners, with the ultimate goal of 

identifying those CAM interventions that have enough evidence 

to support NCI-initiated prospective research. 

NCI Best Case Series Protocol

The NCI Best Case Series (BCS) Protocol received final approval 

from NCI’s Special Studies Institutional Review Board in January 

2011. The BCS Protocol is designed as a retrospective data 

analysis of patients treated with alternative cancer approaches 

in order to assess whether enough information exists to make a 

decision in favor of future NCI-initiated research. Because most 

alternative cancer treatments have not been formally evaluated 

in prospective studies, the NCI BCS Protocol strives to verify 

existing case report data in order to assess whether further 

research on the alternative treatment is warranted.

During FY 2011, 72 cases of cancer patients treated with an 

alternative approach were submitted to the NCI Best Case Series 

Program and reviewed for eligibility. Eleven of these cases met 

the NCI BCS criteria for further review.

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 

publications and web site.

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.

Newsletter on NCI’s CAM Activities

OCCAM’s twice-yearly newsletter, NCI CAM News, provides 

the latest information on NCI-sponsored research, funding 

opportunities, meetings and workshops, as well as educational 

information on cancer and CAM. NCI CAM News also includes 

features on cancer CAM projects representing the full range of 

NCI’s activities as well as OCCAM program updates. 

The newsletter is available online: http://cam.cancer.gov/news_

newsletter.html
10

occam staff list: fy 2011

Jeffrey D. White, M.D., 

Director, OCCAM

Christina Armstrong, 

Administrative Program Specialist

Kisha Anderson, 

Administrative Assistant

Libin Jia, M.D., 

Health Scientist Administrator

Isis Mikhail, M.D., Dr.P.H., M.P.H.,

Director, Extramural Research Program

Dan Xi, Ph.D., 

Program Officer, 

Research Development and Support Program

Miriam Al Keliddar, M.P.H., 

Cancer Research Training Award Fellow 

Farah Zeba Zia, M.D., 

Director, Case Review and Intramural Science Program

Oluwadamilola Olaku, M.D., M.P.H., 

Program Coordinator, Case Review 

and Intramural Science Program

Jeans Santana, B.S., 

Cancer Research Training Award Fellow

Elizabeth Austin, M.S., 

Coordinator, Communications and Outreach Program

Barbara McMakin, M.S., 

Communications Analyst, 

Communications and Outreach Program

Rhonda Ragab, M.P.H., 

Health Communications Intern, 

Communications and Outreach Program

nci cam clinical trials

Many CAM approaches are being studied via clinical trials in 

cancer patients. The OCCAM web site hosts a database which 

organizes CAM clinical trials by cancer types and types of 

symptoms. Clicking on an entry in the table triggers a search of 

the NCI’s PDQ® Cancer Clinical Trials Registry, which includes 

approximately 8,000 clinical trials that are open and approved to 

accept patients. The table also archives trials that are currently 

closed. The Registry is available on the NCI web site at http://

www.cancer.gov/clinicaltrials/search/.

There are currently (at time of publication) 79 active NCIsupported cancer CAM clinical trials. See Appendix for the 

complete list.

For the current list of all CAM clinical trials by cancer type and 

to access the CAM clinical trials table, go to http://cam.cancer.

gov/cam/clinicaltrials_table.html.

Note: NCI 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.

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
11

highlights from 

nci’s cam 

training projects

NCI Research in Complementary and Alternative Medicine

The highlights on the following pages are selected from the 27 CAM training 

projects that NCI supported during FY 2011 at laboratories and clinics throughout 

the United States and the world. NCI’s programs allow students and professionals 

at all stages of their careers to develop the skills necessary to conduct basic, clinical, 

and cancer control research into CAM therapies and interventions.

Abstracts for the CAM training projects featured in the report can be found by searching the project or grant number in the 

NIH RePORTER research trials database. 
12

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011

Testing Vegetable Compounds to Boost 

Breast Cancer Survival

center for cancer training

The relatively minimal side effects of most dietary interventions for primary cancer prevention, as well as for 

prevention of cancer recurrence, make such approaches 

appealing to cancer researchers. Li Tang, Ph.D., an Assistant Professor of Oncology at Roswell Park Cancer Institute, has focused 

her career on studying the anti-cancer properties of isothiocyanates, a group of naturally occurring phytochemicals found in 

cruciferous vegetables such as broccoli, cauliflower, and cabbage.

As a post-doctoral researcher, Dr. Tang used both epidemiology 

and laboratory approaches to explore whether a diet high in 

cruciferous vegetables helps prevent the development of bladder 

cancer or its recurrence. She also sought to understand how 

isothiocyanates affect cancer cells on a molecular level.

In the epidemiology studies, Dr. Tang and her colleagues found 

a strong association between a diet high in raw cruciferous 

vegetables and both a reduced risk of bladder cancer and 

increased survival after bladder cancer treatment. 

Studies from other laboratories suggested these effects may be 

due to the way the body processes isothiocyanates, Dr. Tang 

explained, noting that the active compounds from the vegetables 

accumulate in the urine, which is excreted from the bladder. In 

molecular studies*, she and her colleagues teased out some of the 

reasons that this accumulation could be beneficial to the bladder. 

They found that isothiocyanates, at the levels found in the bladder, 

both arrest the cell cycle in cancerous cells – stopping them from 

dividing – and induce apoptosis, which causes cells to die.

Dr. Tang became interested in whether the isothiocyanates could 

have preventive effects in other organs, where the doses would 

not be as high as in the bladder. In 2011, she received an NCI 

career development award** to extend her work to breast cancer, 

using both epidemiology and clinical studies. 

“For bladder and breast cancer, we’re looking at two different 

scenarios” for how the isothiocyanates may induce their anticancer effects, said Dr. Tang. Isothiocyanates do not accumulate 

in breast tissue at levels that could stop cell growth or cause cell 

death, but research from Dr. Tang’s and other labs has shown 

that the isothiocyanates may change the expression of the 

estrogen receptor in breast cancer cells. For breast cancers that 

express the estrogen receptor – about two-thirds of all tumors 

in the breast – the receptor can help feed cancer cell growth. 

Therefore, blocking the estrogen receptor is a target of modern 

hormone therapy for breast cancer, including tamoxifen and the 

selective estrogen receptor down-regulator, fulvestrant.

With her award, Dr. Tang is planning a randomized, presurgical study with 50 female breast cancer patients to see if 

isothiocyanates given orally – in the form of broccoli sprout 

extract produced at the Johns Hopkins University – can reduce 

expression of the estrogen receptor and change the expression of 

several genes that indicate breast cancer characteristics (such as 

aggressiveness). Because the usual time period between a biopsy 

for diagnosis of breast cancer and surgery is about 2 to 3 weeks, 

Dr. Tang and her colleagues can use that period of time – and 

tissue samples taken during the biopsy and surgery – for their 

biomarker study of isothiocyanates’ effects without interfering 

with the standard treatment. They plan to start enrolling 

participants by the end of 2012.

“We want to look at these biomarker changes to see whether 

isothiocyanates may be used long term to modulate breastcancer survival,” explained Dr. Tang. Additional epidemiological 

information will be gathered through collaboration with the 

Pathways Study, an ongoing, prospective study of breast cancer 

survivors within the Kaiser Permanente Northern California 

Health System. This collaboration will provide information on 

diet, survival, and genetic profiles of breast tumors from over 

3,800 women.

If their preliminary work yields positive results, Dr. Tang hopes 

to initiate a long-term, randomized trial testing whether an 

interview-based intervention can boost intake of cruciferous 

vegetables in breast cancer survivors, and whether that increased 

vegetable consumption “would have a long-term effect on breastcancer survival.” 

* Tang, L., & Zhang, Y. (2004). Dietary isothiocyanates inhibit the growth of human 

bladder carcinoma cells. Journal of Nutrition, 134, 2004-10. 

* Bhattacharya, A., Tang, L., Li, Y., Geng, F., Paonessa, J. D., Chen, S. C., Wong, 

M. K., & Zhang, Y. (2010). Inhibition of bladder cancer development by allyl 

isothiocyanate. Carcinogenesis, 31, 281-86.

** Grant number: 1K07CA148888-01A1
13

highl igh ts from nci's c a m t r a ining projec ts

Tomato and Soy Combination Studied 

for Prostate Cancer Prevention

center to reduce cancer health disparities

Krystle Zuniga, a Ph.D. candidate at University of Illinois 

at Urbana-Champaign (UI-UC), has always been 

interested in nutrition and learning how various whole 

foods can have an impact on cancer prevention.

Ms. Zuniga is a recipient of an NCI Ruth L. Kirschstein 

National Research Service Award* for Individual Pre-doctoral 

Fellowships to Promote Diversity in Health-Related Research 

(F31), which is a component of the Continuing Umbrella of 

Research Experiences (CURE) program at NCI. This fellowship 

provides Ms. Zuniga with funding support to complete her 

Ph.D. training in Nutritional Science at the UI-UC and to 

pursue her goal of becoming a translational researcher in the 

field of diet and cancer. 

In her predoctoral training, Ms. Zuniga – under the mentoring of 

Steven Clinton, M.D., Ph.D., at The Ohio State University (OSU) 

– investigated the bioavailability of soy-based compounds, such 

as isoflavones, and tomato phytochemicals, such as carotenoids, 

in animal models. Her research on the combination of these 

foods in rats for prevention of prostate cancer led to Ms. Zuniga’s 

first peer-reviewed publication**. She was also excited to work 

with clinical collaborators at OSU “who are trying to look at the 

combination of soy and tomato products in human clinical trials,” 

she recalled. “Then we really became interested in finding the 

optimal combination of those foods for cancer prevention.”

Ms. Zuniga is currently pursuing her interest in research to 

quantitatively define and understand the mechanisms by which 

consumption of soy or tomato products, alone or together, may 

reduce the risk of prostate cancer. “The objective is to investigate 

the effects of soy germ- and/or tomato powder-containing diets 

on the progression of prostate cancer in the TRAMP (Transgenic 

Adenocarcinoma of Mouse Prostate) model,” she noted.

Based on findings from her previous animal study, Ms. Zuniga 

hypothesized that combining soy and tomato may not be as 

effective in preventing cancer as are diets that used soy or tomato 

alone. “We found less carotenoid accumulation in the prostate, 

liver, and other organs in the rats that received both tomato 

and soy,” she said. “So we were worried there was a negative 

interaction of the two foods in the animals and that less of the 

compounds were getting into the tissues of interest and maybe 

making the combination less protective.”

Although her current study in the TRAMP model found similarly 

lower levels of carotenoids in tissues from the combination diet, 

nonetheless, the mice who ate both soy and tomato powder did 

better in terms of the progression of prostate cancer, Ms. Zuniga 

reported, compared with mice who were fed only one of the foods, 

and compared to the control group who ate neither. She plans to 

publish her findings in the near future.

“I think it’s exciting that this intervention is able to have this 

much of an effect in a very aggressive model of prostate cancer in 

mice,” Ms. Zuniga noted. Because most prostate cancers in men 

are slow growing, “the type of effect such a dietary combination 

could have in humans could be pretty significant as well.” The 

use of a whole-foods approach for cancer prevention also avoids 

many of the safety concerns from traditional chemoprevention by 

using large doses of single compounds extracted from plants and 

other sources, she said.

The NCI fellowship grant “has been helpful to my career,” Ms. 

Zuniga commented. “I was really excited to get funded to do this 

type of project in nutrition and cancer prevention.” 

* Grant number: 1F31CA153804-01A1

** Zuniga K., & Erdman J. (2011). Combined consumption of soy germ and tomato 

powders results in altered isoflavone and carotenoid bioavailability in rats. Journal of 

Agricultural and Food Chemistry, 59, 5335-41. 
highlights from

nci’s cam research

Understanding the Causes and Mechanisms of Cancer

14

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.
15

highl igh ts from nci's c a m r ese a rch

Coffee Drinking Not Unhealthy and is 

Possibly Associated with Lower Risk of Death

division of cancer epidemiology and genetics

Coffee is one of the most widely consumed beverages in 

the United States and worldwide, but the association 

between coffee consumption and the risk of death 

remains unclear, with previous studies yielding mixed results. A 

recent analysis by NCI researchers of data from the NIH-AARP 

Diet and Health Study, a large study of older adults, suggests 

that coffee drinking may be associated with a lower risk of death 

for most diseases and other causes. However, they did not find a 

lower risk of death by cancer among coffee drinkers.

The analysis*, by researchers from NCI’s Division of Cancer Epidemiology and Genetics (DCEG), showed that people who reported that they drank coffee (whether caffeinated or decaffeinated), 

had a slightly lower risk of death from heart disease, respiratory 

disease, stroke, injuries and accidents, diabetes, and infections 

than those who did not report drinking coffee. 

The NCI researchers observed these results among study 

participants after adjusting for the effects of other risk factors 

on mortality, such as smoking and alcohol consumption. The 

scientists cautioned, however, that they can’t be sure whether 

these associations mean that drinking coffee actually makes 

people live longer.

“A few recent studies have suggested that people [who drink 

coffee] have a slightly lower risk of death,” explained Neal 

Freedman, Ph.D., M.P.H., who led the new analysis within 

DCEG. “Because it was a very modest effect, we wanted to look 

at this in a really big population cohort like NIH-AARP study, 

[which enabled us] to look for even modest associations between 

coffee drinking and different causes of death.”

Dr. Freedman noted, “There has been a lot of concern that 

drinking coffee was not a healthy thing to do. Some people 

describe coffee drinking as their ‘guilty pleasure.’ Although we 

cannot infer a causal relationship between coffee drinking and 

lower risk of death, we believe these new results do provide some 

reassurance that coffee drinking does not adversely affect health.”

Dr. Freedman and his colleagues examined the association 

between coffee drinking and risk of death in 400,000 U.S. men 

and women ages 50 to 71, who participated in the NIH-AARP 

study. Researchers collected information about coffee intake 

once by questionnaire at study entry in 1995–1996, and followed 

the participants until their date of death or December 31, 2008, 

whichever came first. More than 52,000 participants died during 

the study period.

The researchers found that the association between coffee and 

reduction in risk of death increased with the amount of coffee 

consumed. Compared with men and women who did not drink 

coffee, those who consumed three or more cups of coffee per 

day had an approximately 10% lower risk of death. In addition, 

the DCEG scientists found that coffee drinking was not 

associated with increased cancer mortality among women, but 

did find a slight, and only marginally statistically significant, 

association of heavier coffee intake with increased risk of 

cancer death among men.

Dr. Freedman cautioned that in the NIH-AARP study the 

amount of coffee consumption was assessed by self-report at only 

a single time point and therefore might not reflect long-term 

patterns of actual coffee intake by the study participants. Also, 

information was not available to researchers on how the coffee 

was prepared (espresso, boiled, or filtered). The NCI scientists 

consider it likely that coffee preparation methods affect the levels 

of different components in the coffee consumed. Dr. Freedman 

said that DCEG researchers hope to examine these factors in 

future studies.

 “The mechanism by which coffee protects against risk of death 

– if indeed the finding reflects a causal relationship – is not clear,

because coffee contains an estimated 1,000 different compounds 

that might potentially affect health,” Dr. Freedman added.

Another recent analysis of data from the NIH-AARP study, 

led by Rashmi Sinha, Ph.D., also of NCI’s DCEG, indicated 

that people who drank four or more cups of coffee (caffeinated 

or decaffeinated) per day had a lower risk of colon cancer 
16

incidence**, particularly cancers of the region known as the 

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011

proximal colon. DCEG researchers also recently reported an 

inverse association between coffee drinking and endometrial 

cancer*** but found no association between coffee consumption 

and breast cancer risk among the NIH-AARP study 

participants****.

* Project number: Z01CP010196

** Sinha, R., Cross, A.J., Daniel, C.R., Graubard, B.I., Wu, J.W., Hollenbeck, A.R., ... 

Freedman, N.D. (2012). Caffeinated and decaffeinated coffee and tea intakes and risk 

of colon cancer larger prospective study. American Journal of Clinical Nutrition, 96(2), 

374-381.

*** Gunter, M.J., Schaub, J.A., Xue, X., Freedman, N.D., Gaudet, M.M., Rohan, T.E., 

Hollenbeck, A.R., & Sinha, R. (2012). A prospective investigation of coffee drinking 

and endometrial cancer incidence. International Journal of Cancer, 131(4), E530-536. 

**** Gierach, G.L., Freedman, N.D., Andaya, A., Hollenbeck, A.R., Park, Y., 

Schatzkin, A., & Brinton, L.A. (2012). Coffee intake and breast cancer risk in the NIHAARP diet and health study cohort. International Journal of Cancer, 131(2), 452-460. 

Researcher Investigates a Vitamin’s 

Potential Dual Effect on Cancer

division of cancer biology

Folate, a B vitamin, is essential for the normal functioning 

of the body. A shortage of folate in the diet can cause 

many problems, most notably birth defects such as spina 

bifida in children born to mothers with low levels of folate 

during early pregnancy. 

In the 1990s, to reduce the number of children born with birth 

defects many countries, including the United States, mandated 

that flour and other grain products – such as pasta and cereal 

– be fortified with folate. In addition to consuming fortified 

foods, many people receive substantial amounts of the dietary 

compound through the use of vitamin supplements. 

Since a low intake of folate in the diet can also increase the risk of 

cancer, particularly colorectal cancer, on first glance it seems that 

maximizing the intake of folate could only be a good thing. But 

Joel Mason, M.D., professor in the Friedman School of Nutrition 

Science and Policy at Tufts University, who has devoted his career 

to studying the effects of dietary folate and cancer, urges caution 

about this positive assessment.

“It’s pretty much well accepted as a scientific fact now that 

habitual under-consumption of folate leads to an increased risk of 

cancer,” Dr. Mason noted. “But interestingly, one of the things we 

noticed in several of our animal models is that there seemed to be 

a bi-modal effect of folate: if we gave inadequate amounts of folate 

to our animals it would increase tumor formation. On the other 

hand, when we gave them large quantities of folate – levels of 

dietary folate that were way beyond the basal requirements – we 

would sometimes see a promotion of cancer.”

This unexpected finding is not as paradoxical as it seems, Dr. 

Mason said. Folate serves as an essential growth factor for 

dividing cells because the vitamin participates in the biochemical 

reaction that produces the nucleotide thymidine, one of the 

four building blocks of DNA, he explained. A lack of thymidine 

interferes with healthy DNA synthesis and appropriate cell 

division, Dr. Mason continued, but a flood of thymidine, as could 

be provided by excess folate, could potentially help fuel rapidly 

dividing cancer cells.

In 2007, Dr. Mason and his colleagues published a paper* 

hypothesizing that colorectal cancer incidence in the United States 

and Canada experienced a spike about a year after the introduction 

of mandatory folate fortification, reversing a 20-year trend of 

decline. “While this epidemiologic data is by no means proof of 

causality, it’s rather interesting and provocative,” said Dr. Mason. 

After participating in a meeting convened by the European 

Food Safety Authority, which found the evidence inadequate to 

determine whether or not excess folate could increase the risk 

of cancer, Dr. Mason decided to further study the issue in a new 

animal model of colorectal cancer. “These types of studies can’t 

ethically be done in humans, so [after the European meeting] 

there was an acknowledgment that to really determine whether 

this hypothetical risk is genuine in the human population it was 

going to require some modeling in animals,” he recounted.

A colleague at Tufts, Kenneth Hung, M.D., had recently developed 

a new mouse model of colon cancer, called the GEM-1 mouse, 

which proved to be ideal for studying the effects of folate on colon 

cancer growth. The model has several advantages over older, 

more widely used models, explained Dr. Mason. One advantage is 

that the GEM-1 mouse develops tumors in the actual colon, also 

known as the large intestine. Most other mouse models of colon 
17

highl igh ts from nci's c a m r ese a rch

cancer develop tumors 

in the small intestine, 

which has a different 

biology from the colon, 

he noted. 

A second advantage is 

that the GEM-1 mouse 

develops all its tumors 

in the distal (lower) 

half of the colon, which 

can be reached using 

a micro-colonoscope 

created by Dr. Hung. This allows tumor growth to be measured 

on an ongoing basis in live animals. Finally, the mutation driving 

colon cancer formation in the GEM-1 mouse is only found in the 

cells lining the distal colon, as would be found in colon cancer in 

people, Dr. Mason added. Most other models contain a germline 

mutation — meaning it would be found in every cell of the body 

— which does not replicate most cases of colon cancer.

With NCI support for his ongoing experiments**, Dr. Mason is 

feeding mice either a diet with a regular level of folate or a diet 

with nine times the amount of folate required for basic body 

functioning, an amount easily achieved in people eating a number 

of fortified foods and taking vitamin supplements, he explained. 

With the micro-colonoscope, “we can actually watch the growth of 

tumors over time, and see if they have accelerated growth in those 

mice taking extraordinarily large amounts of folate.”

As part of the experiments, some of the mice will receive the 

naturally occurring form of folate, and some will receive folic 

acid — the artificial, shelf-stable form of the vitamin used in 

fortification (natural folate breaks down quickly, making it 

unsuitable for fortification and use in supplements). This will 

hopefully shed some light on another unresolved question — 

whether folic acid rather than natural folate is the substance that 

can accelerate cancer growth, Dr. Mason said.

Folic acid quickly saturates the body’s system that coverts it to the 

natural form of the vitamin. As little as half the amount found 

in a typical multivitamin overwhelms the system, leading to folic 

acid spilling into the circulation, explained Dr. Mason. 

“If you insert naturally occurring forms of folate into 

[metabolism], it has to go through several regulatory steps 

that help control how much folate is getting utilized for DNA 

synthesis,” Dr. Mason continued. “When you give folic acid, it 

gets inserted into folate metabolism in a way that can directly be 

used for the synthesis of DNA.”

As part of the experiments, the researchers will be comparing the 

thymidine content within the lining of the colon between mice 

given natural and artificial folate, to see if the artificial form may 

be providing more material for dividing cells.

* Mason J.B., Dickstein A., Jacques P.F., Haggarty P., Selhub J., Dallal G., & 

Rosenberg I.H. (2007). A temporal association between folic acid fortification and 

an increase in colorectal cancer rates may be illuminating important biological 

principles: A hypothesis. Cancer Epidemiology Biomarkers Prevention, 16(7), 1325-9.

** Grant number: 5R21CA150118-02

Evidence Emerges for the Health Risks 

of Sedentary Behavior

division of cancer epidemiology and genetics

At home, at work, and in the community, people today 

are moving less and sitting more than previous 

generations, and researchers are just beginning 

to understand the health risks associated with these behavior 

trends. Until recently, population-based research focused on the 

adverse effects associated with inadequate levels of exercise. But 

the latest evidence suggests that too much sitting – sedentary 

behavior – also has ill effects, and that these effects are distinct 

from those of too little exercise.

One researcher studying these issues is Charles Matthews, 

Ph.D., a physical activity epidemiologist in NCI’s Division of 

Cancer Epidemiology and Genetics. He and his colleagues used 

information from the NIH-AARP Diet and Health Study, which 

was developed at NCI, to examine the independent effects of 

sedentary behavior and exercise on the risk of death due to 

various causes, including cancer.
18

The researchers found 

that prolonged television 

viewing and overall sitting 

time were associated 

with an increased risk of 

death (mortality) from all 

causes. Higher amounts 

of television viewing were 

also linked to an increased 

risk of death from 

cardiovascular disease 

and cancer. Compared 

with those who reported 

watching less than 1 

hour of television per day, 

people who watched 7 or 

more hours per day had a 

60% greater risk of dying 

from all causes, nearly 

twice the risk of death due to cardiovascular disease, and a 20% 

greater risk of death due to cancer.

“Our study was one of the larger studies, and one of only a 

handful, that has shown evidence of a link between sedentary 

behavior and cancer mortality,” Dr. Matthews noted. Other 

reports from the NIH-AARP study have demonstrated links 

between sedentary behavior and increased risks of colon and 

endometrial cancer in particular, he added.

“Probably the most striking thing we saw was that even among 

people who reported 4 to 7 hours a week of exercise, those who 

also reported 5 or 6 hours per day of television viewing still 

had an increased likelihood of death from all causes and from 

cardiovascular disease compared to individuals who reported less 

than an hour a day of television viewing,” Dr. Matthews said. In 

other words, “in terms of the risk for death, participating in a fair 

amount of exercise each week doesn’t completely inoculate you 

against the deleterious effects of spending a lot of time in front of 

the television set.”

The researchers followed more than 240,000 participants in the 

NIH-AARP Diet and Health Study, age 50–71 years old at the 

start of the study, for an average of 8.5 years. At the start of the 

study, the participants reported their average daily television 

or video viewing time, overall sitting time in the past year, and 

the average amount of leisure time per week spent in moderate 

to vigorous physical activity, or exercise, over the past 10 years. 

Examples of moderate to vigorous physical activity included 

walking for exercise, running or jogging, swimming laps, and 

heavier lawn and garden work.

Dr. Matthews explained that, in this study, prolonged time in 

front of the television was more strongly linked with increased 

mortality than overall sitting time because a single question that 

asks how long people spend sitting each day overall is probably 

not reported as accurately as a single question about a specific 

sitting behavior, in this case television viewing.

“Our results add to the growing evidence that the adverse effects 

of sedentary behavior seem to be independent of the benefits of 

exercise,” Dr. Matthews said. The finding, he noted, “opens the 

door for developing new strategies to increase the overall activity 

level of the population by reducing sedentary time in favor of 

more active pursuits. To date, our primary strategy has been to 

encourage exercise participation.”

“It’s really a wake-up call to think about all of the many different 

places you sit during daily life and [try to] switch to an upright 

and active approach to doing those same activities,” Dr. Matthews 

continued. For instance, he added, at home “you can stand up 

to fold laundry or cook meals. You can rearrange your computer 

workstation so you are able to stand [at the computer].” Taking 

frequent breaks to walk around the room, house, or office may 

also be helpful, he said.

The NCI researchers found that their results didn’t change 

much when they adjusted for Body Mass Index (BMI), which is 

a measure of obesity, suggesting that factors other than obesity 

account for the ill effects of sedentary behavior.

Dr. Matthews and his colleagues are now analyzing information 

from more detailed questionnaires that were administered as 

part of the NIH-AARP Diet and Health Study to find out how 

much and what types of activity can minimize the health risks 

associated with sedentary behavior, including activities such as 

household chores, lawn and garden work, caring for children and 

elders, and home repairs.

Project number: Z1A CP 010197

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
19

accelerating 

progress in 

cancer prevention

Prevention is our first line of defense against cancer. Efforts to prevent cancer 

focus on understanding and modifying behaviors that increase risk, mitigating 

the influence of genetic and environmental risk factors, and interrupting cancercausing processes through early medical intervention.
20

Finding a Healthy Dietary Ratio for 

Prostate Cancer Prevention

division of cancer prevention

The leading cause of mortality for the 10 percent of 

patients who develop recurrent or refractory (treatment 

resistant) prostate cancer is due to the progression of 

prostate cancer to androgen independence — the ability of the 

tumor to grow even in the absence of androgens, hormones that 

can stimulate the growth of prostate cancer cells. Strategies that 

prevent this progression are greatly needed, and early studies 

conducted by Linda A. deGraffenried, Ph.D., Associate Professor 

and Associate Chair of the Department of Nutritional Sciences 

at The University of Texas at Austin, demonstrate how the 

mammalian target of rapamycin (mTOR) — a protein regulator 

of cell growth — could play a role in controlling the progression 

of prostate cancer to androgen independence in animal models. 

Several anti-cancer agents that target the mTOR pathway are 

currently in clinical development. “Because the mTOR pathway 

is regulated by growth factors and nutrients, this suggests that 

natural dietary interventions could also have protective effects 

against cancer through regulation of this pathway,” said Dr. 

deGraffenried. “We set out to examine the impact of a variety 

of dietary interventions that could prove beneficial for prostate 

cancer patients by targeting this pathway, including omega-3 and 

omega-6 fatty acids*.”

Omega-3 and omega-6 fatty acids are found naturally in the 

human diet through the consumption of cold water fish, and 

seeds and nuts and the oils extracted from them, respectively. 

In a preliminary study using an in vitro model of androgen 

suppression, Dr. deGraffenried and colleagues discovered that 

the balance between omega-3 and omega-6 fatty acids plays a role 

in affecting the progression of prostate cancer**. Specifically, 

the omega-3 fatty acid docosahexaenoic acid (DHA) effectively 

delayed the progression of prostate cancer cells to an androgenindependent state, whereas the omega-6 fatty acid arachidonic 

acid (AA) promoted disease progression. “Additionally, this delay 

in progression to hormone-refractory disease was mediated in 

part through inhibition of the mTOR signaling pathway,” said 

Dr. deGraffenried. 

The American Heart Association (AHA) recommends an 

omega-6 to omega-3 ratio of 10:1; unfortunately, those on a 

Western diet eat too much omega-6 and not enough omega-3. 

“In men consuming a Western diet, the ratio is approximately 

46:1 because omega-6 levels are high in processed foods; in the 

Asian diet, on the other hand, the ratio is 1.3:1 because omega-3 

levels are high in fish,” said Dr. deGraffenried. “And if you look 

at the incidence of both breast and prostate cancer in the Asian 

population, it is very, very low.”

From a dietary perspective, Dr. deGraffenried and colleagues 

are trying to determine the best fatty acid ratio for preventing 

the progression of prostate cancer in patients. Specifically, does 

the AHA recommendation (10:1) provide the same benefit for 

prostate cancer as it does for cardiac protection? Or is the Asian 

diet ratio (1.3:1) required for maximal protection?

Early in vivo data suggest that the AHA recommendation of 10:1 

provides the same protective benefit for prostate cancer as does 

an Asian diet. “In addition, our data shows that (blood) serum 

levels serve as effective surrogate markers as they closely reflect 

the levels of fatty acids that are getting into the tumors,” said 

Dr. deGraffenried. 

The challenge, however, is getting patients to modify their fatty 

acid ratio from 46:1 to 10:1 through diet alone because eating 

patterns are notoriously difficult to overcome. “The strategy will 

be to provide fatty acid supplements to patients based on their 

serum levels, and to adjust the supplements as needed over time 

to maintain the proper ratios,” said Dr. deGraffenried. 

NCI Division of Cancer Prevention Program Director Young 

Kim, Ph.D., commented, “Dr. deGraffenried’s group is revealing 

the mechanisms by which an omega-6 to omega-3 fatty acid ratio 

affects the outcome in prostate cancer patients. This information 

will be important for the development of effective dietary 

intervention strategies that improve overall survival.”

* Grant number: 5R01CA118962-05

** Friedrichs, W., Ruparel, S.B., Marciniak, R.A., & deGraffenried, L. (2011). Omega-3 

fatty acid inhibition of prostate cancer progression to hormone independence is 

associated with suppression of mTOR signaling and androgen receptor expression. 

Nutrition and Cancer, 63(5), 771-777.

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
21

accel er at ing progr ess in c a ncer pr e v en t ion

Complementary Strategies for Prostate Cancer 

Prevention and Management

division of cancer prevention

Prostate cancer is the most common cancer diagnosis and 

the second deadliest cancer among men in the United 

States. Additionally, men living in Western countries 

are six times more likely to be diagnosed with prostate cancer 

compared to the rest of the world. This discrepancy has been 

in part attributed to differences in dietary intake as men in 

developing countries, who adopt a Western diet, experience 

a greater incidence of prostate cancer. It is unclear, however, 

whether the increased risk associated with a Western diet is due 

to a greater intake of fat, carbohydrates, or total calories. 

With NCI funding*, Stephen J. Freedland, M.D., Associate 

Professor of Surgery and Pathology in the Department of Surgery 

at Duke University School of Medicine, has been studying 

the impact of both carbohydrate and fat intake on prostate 

cancer biology with the goal of developing novel, non-toxic 

complementary treatments, including dietary modification and 

phytopharmaceuticals (plant-based drugs), aimed at slowing 

prostate cancer progression. Dr. Freedland and colleagues had 

previously shown that mice fed a no-carbohydrate ketogenic diet 

(NCKD: 84% fat–0% carbohydrate–16% protein) demonstrated 

significantly reduced prostate tumor growth (~30%) and 

prolonged survival compared to mice fed a Western diet**. 

“Mice consuming NCKD also had a decrease in signaling of the 

insulin-like growth factor (IGF) pathway, which is known to be 

involved in prostate cancer progress and this was confirmed in 

follow up studies,” said Dr. Freedland. “The problem is that a zero 

carbohydrate diet is not feasible for humans. So the question was: 

how low is low? Would a low-carbohydrate diet, similar to that of 

the Atkins diet, provide the same protective benefits as NCKD?”

The first set of studies demonstrates that mice consuming 

less restrictive low-carbohydrate diets (10% to 20% kcal 

carbohydrates) have similar tumor growth, overall survival, and 

IGF signaling as mice fed NCKD***. “The results of these data 

are now being tested in clinical studies and approximately 30 

men are already enrolled ,” said Dr. Freedland. “A second 

study, funded by NCI** ***, is set to open early next year.” 

The challenge is that a behavioral change such as diet is 

notoriously difficult to implement in both healthy individuals 

and sick patients, regardless of the diet being tested. Men on 

a Western diet typically consume 30-40% of their total caloric 

intake from fat and epidemiological and experimental data 

suggest consuming higher levels of dietary fat may negatively 

impact prostate cancer progression. It remains unknown, 

however, whether total fat or the cholesterol found in fat sources 

is associated with disease progression, as excess dietary fat is 

linked to high-serum cholesterol levels. 

In a separate study, Dr. Freedland and colleagues searched 

for natural dietary interventions, including resveratrol and 

pomegranate that could be added to a Western diet to slow tumor 

growth; however, it was found that neither of these interventions 

had an impact. What they did find was that blocking cholesterol 

uptake with a cholesterol-lowering drug proved effective in 

slowing the growth of aggressive tumors.

In two independent studies, Dr. Freedland and colleagues 

demonstrated that daily treatment with the cholesterol-uptake 

inhibitor ezetimibe (Zetia®) delayed the rapid development of 

prostate cancer in animal models that mimic aggressive disease 

in humans. Although ezetimibe appeared to slow the growth of 

aggressive prostate tumors, this intervention did not impact slowgrowing tumors.

NCI Division of Cancer Prevention Program Director Young 

Kim, Ph.D., commented, “When these mice are fed a high-fat diet 

that is linked to high-serum cholesterol levels (a typical Western 

diet), blocking cholesterol uptake significantly reduces the size 

of the prostate cancer. Dr. Freedland’s group is providing new 

insight into the use of cholesterol-lowering agents as prevention 

for aggressive prostate cancer.” 

* Grant number: 5R01CA131235-05

** Freedland, S.J., Mavropoulos, J., Wang, A., Darshan, M., Demark-Wahnefried, 

W., Aronson, W.J., ... Issacs, W.B. (2008). Carbohydrate restriction, prostate cancer 

growth, and the insulin-like growth factor axis. Prostate, 1(68), 11-19. 

** Mavropoulos, J.C., Buschemeyer, W.C. 3rd, Tewari, A.K., Rokhfeld, D., Pollak, M., 

Zhao, Y., ... Freedland, S.J. (2009). The effects of varying dietary carbohydrate and 

fat content on survival in a murine LNCaP prostate cancer xenograft model. 

Cancer Prevention Research, 2(6), 557-565. 

*** Masko, E.M., Thomas, J.A. 2nd, Antonelli, J.A., Lloyd, J.C. Phillips, T.E., Poulton, 

S.H., ... Freedland, S.J. (2010). Low-carbohydrate diets and prostate cancer: how low 

is “low enough?”. Cancer Prevention Research, 3(9), 1124-1131.

  Clinicaltrials.gov identifier: NCT00932672

** *** Grant number: 1K24CA160653-01
22

Plant-Based Chemoprevention Investigated 

for Lung Cancer

division of cancer prevention

Despite extensive anti-smoking campaigns and a 

substantial drop in the number of adult smokers in the 

United States, lung cancer continues to be a disease 

that affects smokers, non-smokers, and even former smokers, 

years after quitting. These substantial, lingering risk factors 

for lung cancer in the population make developing effective 

chemoprevention agents – that prevent cancer from developing or 

progressing into detectible disease – a priority.

Fekadu Kassie, D.V.M, Ph.D., a toxicologist and assistant 

professor of oncology at the University of Minnesota Masonic 

Cancer Center, has chosen to focus his career on identifying 

promising compounds for testing in human lung cancer 

chemoprevention trials. Since 2007, his research team has been 

exploring the anticancer effects of a compound called indole-3-

carbinol (I3C), found in cruciferous vegetables such as broccoli 

and cabbage.

Population-based studies have suggested that people who eat 

more cruciferous vegetables have a lower risk of lung cancer, and 

laboratory experiments with cells and animals show promising 

anticancer activity of I3C. These findings led Dr. Kassie, with 

funding from NCI*, to investigate the molecular mechanisms 

behind the observed effects of I3C, and to determine the dose of 

I3C for use in early-phase human chemoprevention trials.

The safety of I3C has been well established, explained Dr. Kassie: 

“No toxic or undesirable effects of these vegetables are reported 

in Asian countries where they’re consumed at high levels. The 

dietary intake of I3C among populations in these countries is 

close to the dose found to be safe in clinical trials.” 

In their earlier mouse studies, administration of I3C, or a 

dimer of I3C that develops in the gastrointestinal tract called 

3,3’-diindolylmethane (DIM), reduced the number of tobacco 

smoke carcinogen-induced mouse lung tumors by 60%-80%. 

This experimental model mimics the condition of current 

smokers since administration of I3C was begun during 

carcinogen treatment. 

In addition, experiments revealed that exposure to the carcinogen 

resulted in changes in the expression of several proteins 

associated with tumor formation, including cell division and 

avoidance of normal, programmed cell death. According to Dr. 

Kassie, administering I3C along with the carcinogen blocked 

some of these changes.

Further mouse studies designed to mimic chemoprevention in 

former smokers showed that I3C also reduced the number of 

small lung tumors formed after carcinogen exposure by about 

75% at a high dose**, Dr. Kassie noted. Additional protein 

expression studies suggested that I3C inhibits cell survival and 

division in precancerous and cancerous lung cells, he said. 

Although additional tests suggested that I3C administration after 

precancerous cells and small tumors had already been formed 

could not decrease the number of these smaller tumors, it could 

decrease the number of these early tumors progressing to lung 

adenocarcinoma (a type of lung cancer)***, Dr. Kassie explained.

Dr. Kassie and his colleagues believe that their results warrant 

moving I3C into human studies. They are currently writing a 

grant to obtain funding for an early phase chemoprevention 

trial, which will likely use both I3C and DIM, which have similar 

mechanisms of action in the body.

Marjorie Perloff, M.D., program director with the NCI Division 

of Cancer Prevention, commented: “The studies in this 

grant complement the goals of the Chemopreventive Agent 

Development Research Group to develop new agents for cancer 

prevention. This trial studies a compound derived from a group 

of natural compounds found in cruciferous vegetables which 

purports to be the ‘active’ agent in terms of cancer prevention, 

and is also the source of another agent, 3,3’-diindolylmethane 

(DIM), which has been extensively studied for possible cancer 

preventive activity.”

* Grant number: 5R01CA128801-04

** Kassie F., Matise I., Negia M., Upadhyaya P., & Hecht S.S. (2008). Dose-dependent 

inhibition of tobacco smoke carcinogen-induced lung tumorigenesis in A/J mice by 

indole-3-carbinol. Cancer Prevention Research, 1(7), 568-76.

*** Qian X., Melkamu T., Upadhyaya P., & Kassie F. (2011). Indole-3-carbinol 

inhibited tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice when 

administered during the post-initiation or progression phase of lung tumorigenesis. 

Cancer Letters, 311(1), 57-65.

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
23

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.
24

Antioxidant Enzymes Show Unexpected Behavior 

in Leukemia Cells Treated with Imatinib

division of cancer treatment and diagnosis

FDAapproval of the targeted drug imatinib 

in 2001 revolutionized the treatment of 

chronic myelogenous leukemia (CML), 

changing it from a difficult-to-treat cancer with a poor prognosis 

to a chronic, manageable condition. A long-term, follow-up study 

found that CML patients treated with imatinib, who have been 

in remission for at least two years, have the same risk of death as 

their peers in the general population.

Imatinib targets a specific genetic mutation that causes almost all 

cases of CML. In this mutation – a type known as translocation – 

pieces of two different chromosomes become stuck together and 

produce a protein called BCR-ABL. This protein is like a switch 

stuck in the “on” position: it constantly signals cancer cells to 

divide. Imatinib stops cancer cell growth by blocking BCR-ABL.

Unfortunately, some patients eventually become resistant to 

imatinib, requiring a change in treatment. Alan Diamond, Ph.D., 

professor of pathology at the University of Illinois at Chicago, is 

researching whether antioxidants – substances that protect cells 

from the damage caused by free radicals (also called reactive 

oxygen species, ROS) – contribute to imatinib resistance.

With funding from NCI*, his laboratory has looked at how levels 

of an antioxidant enzyme, glutathione peroxidase-1 (GPx-1), 

change during treatment with imatinib. GPx-1 requires the trace 

element selenium, found naturally in many foods, to work.

Studies from Dr. Diamond’s and other laboratories have found an 

association between lack of selenium in the diet, reduced GPx-1 

activity in the body, and an increased risk of cancer. When he 

read a paper in 2003 that the ABL protein (part of BCR-ABL that 

drives CML) activates GPx-1, “my thought was that [GPx-1] is a 

beneficial protein, and people who have their ABL deactivated by 

therapy [with imatinib] might be suffering,” he said.

Dr. Diamond and colleagues hypothesized that CML patients 

taking imatinib would have decreased GPx-1 activity, and tested 

this idea in blood samples taken before and during treatment 

from seven patients**. Instead of a decrease, “we saw the 

complete opposite,” Dr. Diamond recalled. “The clear trend was 

that levels of GPx-1 were actually higher in the patients being 

treated.”

To look closer at this unexpected finding, Dr. Diamond’s research 

team performed a series of experiments in cultured cancer cells. 

They found that not only do GPx-1 levels increase in the presence 

of the combination of imatinib and the BCR-ABL protein, but 

levels of another important antioxidant enzyme, MnSOD, also 

rise. While GPx-1 levels approximately double in CML cells given 

imatinib, levels of MnSOD rise about five-fold.

Dr. Diamond is currently planning several research projects to 

understand how these newly discovered mechanisms regulate 

important antioxidant genes. The idea that more antioxidants are 

not always better may seem counterintuitive, but makes sense, he 

explained. “Years ago, we thought that antioxidants were always 

a good thing. [But] human epidemiology is now revealing that 

sometimes they’re a good thing and sometimes they’re a bad 

thing.”

“The unproven model is that in the course of your lifetime 

antioxidants can be a very good thing,” Dr. Diamond added. 

“They reduce the chance of carcinogenic mutations. So from 

birth to a certain time in your life, they’re very protective. 

However, once you reach a certain point and cancer is starting 

to develop, at that point these same mechanisms can protect the 

cancer cells.”

An added layer of complexity being studied by Dr. Diamond 

comes from the fact that naturally occurring genetic variations 

– called polymorphisms – can also alter the levels of antioxidant 

enzymes in cells. Extra amounts of these enzymes are not 

necessarily a good thing, even in normal cells. The compounds 

produced when these enzymes break down free radicals are not 

stable. If a cell doesn’t have enough other antioxidant molecules 

from the diet to finish the break-down process, the compounds 

can covert back to the damaging free radicals, Dr. Diamond said. 

“The increase in MnSOD antioxidant enzyme that’s occurring 

in CML may actually be more significant than the increase in 

GPx-1, because a high amount of MnSOD could cause oxidative 

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
25

de v eloping effec t i v e a nd efficien t t r e at men ts

stress,” he explained. Leukemia cells experiencing oxidative 

stress can end up with additional mutations, some of which 

could contribute to resistance to drugs targeting BCR-ABL, Dr. 

Diamond said. 

William D. Merritt, Ph.D., program director at NCI’s Cancer 

Therapy and Evaluation Program, commented: “It is very 

gratifying to see how funding for this small two year discovery 

grant provided a novel link between resistance to a widely-used 

therapeutic for CML, imatinib, and antioxidants, and points to 

the need for further studies to explore changes in antioxidant 

enzymes in patients receiving this and similar therapies.” 

* Grant number: 5R21CA129590-03

** Terry, E. N., Gann, P. H., Molokie, R., Deininger, M., & Diamond, A. M. (2011). 

Changes in the activity of the GPx-1 anti-oxidant selenoenzyme in mononuclear cells 

following imatinib treatment. Leukemia Research, 35(6), 831-3.

High-Fat Diet May Enhance Cancer Patients’ 

Response to Treatments

division of cancer treatment and diagnosis

The goal of cancer treatments such as chemotherapy 

and radiation is to kill cancer cells while minimizing 

damage to healthy cells and tissues. A growing number 

of researchers are studying cancer cell metabolism – that is, the 

chemical processes in the cell that convert or use energy – as 

an avenue to developing new cancer treatments. They hope to 

selectively kill cancer cells by taking advantage of fundamental 

metabolic differences between cancer cells and normal cells.

With support from NCI*, Douglas Spitz, Ph.D., professor and 

director of the Free Radical and Radiation Biology Program at the 

Holden Comprehensive Cancer Center at the University of Iowa, 

along with his colleagues Daniel Berg, M.D. and John Buatti, 

M.D., hope to use a special diet to exploit metabolic differences 

between cancer cells and normal cells to enhance cancer patients’ 

responses to combined chemotherapy and radiation therapy 

(chemo-radio-therapy). 

“Radiation is believed to kill cancer cells by causing the 

formation of free radicals in tumor tissue, inducing a condition 

known as oxidative stress that can be enhanced by chemotherapy 

to achieve better treatment responses,” Dr. Spitz noted. Oxidative 

stress occurs when the balance between cellular anti-oxidants 

and pro-oxidants – free radicals and reactive oxygen species – 

shifts to favor the accumulation of pro-oxidants, he explained. 

If left unchecked, these highly reactive pro-oxidants can damage 

DNA, proteins, and other biological molecules in the cell and 

may cause cell death.

“Tumor cells appear to have disruptions in mitochondrial 

oxidative metabolism that lead them to produce more superoxide 

and other reactive oxygen species, compared with normal 

cells,” Dr. Spitz explained. “Oxidative metabolism is a chemical 

process that occurs in the mitochondria of cells in which oxygen 

consumption is used to make energy from food sources. Altered 

oxidative metabolism in cancer cell mitochondria is thought 

to result in chronic oxidative stress in cancer cells, relative to 

normal cells.”

Ketogenic diets, which are high in fat and low in protein and 

carbohydrates, deprive cells of glucose and force them to rely 

more heavily on mitochondrial oxidative metabolism, Dr. Spitz 

said, adding that healthy cells don’t appear to have the defects in 

mitochondrial metabolic pathways that are present in tumor cells. 

Dr. Spitz is pursuing the idea that “we should be able to induce 

oxidative stress selectively in cancer cells by feeding patients a 

ketogenic diet that forces the use of mitochondrial metabolic 

pathways leading to the production of superoxide.” The 

augmented level of oxidative stress in cancer cells would in turn 

be expected to selectively sensitize cancer cells to conventional 

cancer therapies that kill cells via oxidative stress in an additive 

fashion, he said.

To test the feasibility of this approach, Dr. Spitz and his 

colleagues conducted preliminary studies in mouse models of 

human pancreatic cancer, lung cancer, and head and neck cancer. 

These mice were implanted with human cancer cells and treated 
26

with standard chemo-radio-therapy combinations used clinically 

with and without feeding a ketogenic diet.

“We’ve been able to show that if you feed tumor-bearing mice 

a ketogenic diet, you can inhibit tumor growth and delay the 

progression of disease in animals that have been treated with 

radiation and chemotherapy,” Dr. Spitz reported. The researchers 

also saw an increase in chemical markers of oxidative stress in 

blood samples and tumor samples from animals that were fed the 

ketogenic diet during therapy.

“We think there might be a causal relationship between the 

oxidative stress and the enhanced chemo-radio-therapy responses 

of tumors in animals fed ketogenic diets, but we’re still doing 

experiments to try to prove if that is true,” Dr. Spitz added. 

Meanwhile, in collaboration with his physician colleagues, Dr. 

Spitz has launched an early-phase clinical trial (phase I) in which 

six patients with advanced, inoperable pancreatic cancer and six 

patients with inoperable non-small cell lung cancer (NSCLC) 

will be put on a ketogenic diet for six weeks. The trial will test 

whether patients can safely tolerate the high-fat diet while being 

treated with standard chemo-radio-therapy protocols, he said. 

The researchers will also test blood samples from the patients for 

markers of oxidative stress and ketosis – a state of elevated levels 

of ketone bodies in the body, which would be caused from eating a 

ketogenic diet.

“Ketogenic diets have been used safely for more than 20 years 

for treating epilepsy and we’re only asking people to eat it for six 

weeks,” Dr. Spitz said. If this preliminary clinical trial shows 

that the ketogenic diet is safe for cancer patients, Dr. Spitz and 

his colleagues plan to conduct a clinical trial in a larger number 

of patients with pancreatic cancer and NSCLC. The goal of that 

trial will be to find out whether a ketogenic diet can enhance the 

effectiveness of standard chemo-radio-therapy in humans.

Dr. Dan Xi, the program director at OCCAM responsible for 

overseeing this grant, commented that “using the ketogenic 

diet as adjuvant approach with standard therapies in humans is 

very innovative. This multiple PI grant is led by a strong team 

with proper expertise in both basic and clinical sciences, and 

addresses a research area of special interest for our office and the 

Division of Cancer Treatment and Diagnosis, i.e., complementary 

approaches that augment the therapeutic index of conventional 

cancer therapies.”

* Grant number: 1R21CA161182-01 

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
27

de v eloping effec t i v e a nd efficien t t r e at men ts

Soy Used to Protect Normal Cells While 

Sensitizing Cancer Cells to Radiation

division of cancer treatment and diagnosis

Although radiation therapy can be a powerful treatment 

for lung cancer, normal lung tissue is very sensitive 

to radiation-induced damage. Inflammation of the 

lungs and the formation of scar tissue, which can occur weeks to 

months after treatment, pose particular risks for patients. These 

side effects limit the amount of radiation that can be aimed at 

a lung tumor, potentially decreasing the effectiveness of the 

therapy.

Under a grant from NCI*, Gilda Hillman, Ph.D., professor of 

radiation oncology at Wayne State University and the Barbara 

Ann Karmanos Cancer Institute in Detroit, Michigan, is studying 

whether natural soy isoflavones can both protect normal lung 

cells from radiation damage and increase the toxic effects of 

radiation on lung cancer cells. 

Her research team first asked these questions 12 years ago, in 

collaboration with a colleague at Wayne State, Fazlul Sarkar, 

Ph.D., whose laboratory had been testing natural compounds to 

sensitize cancer cells to chemotherapy drugs. At that time, Dr. 

Hillman’s research focused on combining radiation therapy with 

immunotherapy in several mouse models of cancer. Dr. Sarkar 

suggested that they try combining their areas of research to test 

soy isoflavones with radiation in cancer cells and in her mouse 

cancer models. “I tried it, and it worked!” recounted Dr. Hillman.

Since 2000, her laboratory has painstakingly teased out the details 

of the molecular mechanisms behind the two complementary 

effects observed by combining soy isoflavones and radiation: 

increased cancer cell death and decreased damage to normal 

cells. 

To increase death of cancer cells, the isoflavones found in soy – 

including genistein, daidzein, and glycitein – seem to interfere 

with lung cancer cells’ ability to repair the DNA damage incurred 

from radiation exposure, Dr. Hillman said. In their experiments, 

when she and her colleagues irradiated cancer cells without 

adding soy isoflavones, the cells rapidly activated repair pathways 

that fixed radiation-induced DNA damage, allowing some of the 

cells to live and continue dividing.

When the researchers added soy isoflavones to radiation 

exposure, these repair pathways were inhibited, leading to 

increased cancer cell death, Dr. Hillman explained. This suggests 

that blocking these pathways with soy isoflavones should be 

effective in cancer cells without causing damage to normal cells. 

In fact, soy isoflavones appear to have a protective effect in 

normal lung tissue. In recent mouse studies from Dr. Hillman’s 

laboratory, soy isoflavones given during and after radiation 

therapy reduced bleeding, inflammation, and scarring in normal 

lung tissue in mice treated with radiation**. At the same time, 

“soy increased the killing of tumor cells induced by radiation, 

thus playing a differential role in tumor versus normal cells,” she 

said.

Dr. Hillman and her colleagues are currently planning a trial 

for lung cancer patients, looking at the combination of radiation 

therapy, chemotherapy with the drugs cisplatin and etoposide 

or pemetrexed, and soy. Patients will continue to take soy for 6 

months after treatment, “since studies in our lab have shown 

that the effects of soy are better if you continue it after the end 

of radiation therapy,” explained Dr. Hillman. The researchers 

hope to start the trial after securing a reliable, tested supply of soy 

isoflavone tablets that meet their standards for proof of safety.

NCI Program Director Dan Xi, Ph.D. commented, “This project 

addresses an established research area of special interest 

for complementary approaches that enhance the effects of 

conventional cancer therapies. It is our hope that this study, if 

successful, could ultimately lead to a better therapeutic strategy 

for non-small cell lung cancer care.”

* Grant number: 1R21CA155518-01A1

** Hillman G.G., Singh-Gupta V., Runyan L., Yunker C.K., Rakowski J.T., Sarkar 

F.H., Miller S., Gadgeel S.M., Sethi S., Joiner M.C., & Konski A.A. (2011). Soy 

isoflavones radiosensitize lung cancer while mitigating normal tissue injury. 

Radiotherapy and Oncology, 101(2),329-36.
28

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.
Impact of Exercise on 

Ovarian Cancer Prognosis Studied

division of cancer control and population sciences

Studies suggesting a benefit of physical activity and exercise 

for people with certain cancers, particularly breast cancer, 

are well documented in the medical literature. However, 

very few studies published to date discuss the beneficial effects of 

exercise after a diagnosis of ovarian cancer. Melinda Irwin, Ph.D., 

M.P.H., an epidemiologist at the Yale University School of Public 

Health, is seeking to address that gap with the Women’s Activity 

and Lifestyle Study in Connecticut (WALC).

The need for interventions to improve symptom-control and 

alleviate treatment side effects is critical for ovarian cancer 

patients, Dr. Irwin noted. “When you look at women with ovarian 

cancer, with the treatments they go through and the surgery and 

the later stage of diagnosis, their quality of life (QOL) is often 

significantly impaired,” she said. “I believe exercise will be very 

beneficial for these patients.”

With support from NCI*, Dr. Irwin and her colleagues aim to 

enroll up to 230 sedentary women diagnosed with Stage I-III 

ovarian cancer, who are being randomized for 6 months into 

either a home-based walking program or into an “attention 

control” group who receive weekly health education sessions 

over the phone with a counselor. The counselor also contacts 

the women in the exercise arm of the study by phone, Dr. Irwin 

added. The counselor helps motivate and guide them to complete 

150 minutes of walking per week. 

The walking program intervention used for WALC is designed 

to gradually build in intensity, Dr. Irwin explained. “It’s not as 

though they’re training for a marathon but we’re able to get the 

exercise levels up to exceed the recommended amount of 150 

minutes a week of brisk walking. They wear a heart-rate monitor 

when they exercise and put a pedometer on every day.” Women 

in the exercise group also walk a 1-mile route every month to 

monitor their improvement in walking speed. “When they first 

start the study, it may take some women about 30 minutes to 

walk that mile, but at 2-3 months into it, they might be walking it 

in 20 minutes,” she reported. 

Regular exercise can be challenging for women with latestage ovarian cancer, Dr. Irwin commented. Such patients 

often experience disease recurrence and need to go back on 

chemotherapy. “Some of them also suffer from peripheral 

neuropathy, so they have a fear of falling,” she added. “We 

recommend they use the Nordic walking poles to help with 

balance when they need to and until that fear of falling subsides 

and they’re more confident.” 

There are a number of approaches and strategies the researchers 

use to make it easier for women to continue in the exercise 

program, Dr. Irwin added, and so far, “there is never a woman 

who comes back from an exercise session who says she doesn’t 

feel good.” 

Measuring and comparing the impact of exercise, versus the 

health education control group, on the patients’ QOL (such as 

fatigue, anxiety, and depression) “is the primary endpoint in 

our study,” Dr. Irwin continued. In addition, the researchers 

are conducting baseline and 6-month clinic visits for study 

participants to evaluate the patients’ QOL and surrogate 

biomarkers for ovarian cancer progression, Dr. Irwin added.

“We’re collecting fasting blood samples at the beginning and at 

the end of the study because there are some serum markers, such 

as leptin and insulin-like growth factors (IGFs), that we know are 

related to ovarian cancer that have also been shown to be related 

to exercise or body weight,” Dr. Irwin noted. The researchers will 

assess any changes to these biomarkers, in both the exercise and 

control groups, at the end of the 6-month intervention period.

The study, which is expected to end in 2014, has been expanded 

to include enrollment of patients from outside of Connecticut, Dr. 

Irwin said. She plans to submit an abstract and possibly present 

preliminary findings from the study at the 2013 American Society 

of Clinical Oncology (ASCO) Annual Meeting. If the findings 

show a positive impact of exercise on ovarian cancer patients’ QOL 

and disease biomarkers, Dr. Irwin hopes to conduct a follow-up 

investigation to assess its long-term (3-5 years) effects on disease 

progression and survival among these patients.

29

improv ing t he qua l i t y of l ife for c a ncer pat ien ts, surv i vors, a nd t heir fa mil ies
30

Currently, only about one-third of cancer centers in the United 

States offer some sort of exercise program to their patients 

and cancer survivors, Dr. Irwin commented, and often such 

programs are tailored for or limited to breast cancer patients. 

She hopes to add to the evidence base that opens up exercise 

interventions to more cancer patients, including women with 

ovarian cancer. “If we show that WALC is an effective program 

when done over the phone, it could easily be done and replicated 

nationally,” she commented. 

Catherine M. Alfano, Ph.D., deputy director NCI Office of Cancer 

Survivorship, commented: “Dr. Irwin’s study addresses an 

important gap in NCI’s grant portfolio of exercise and survivorship 

studies that have almost exclusively focused on women with breast 

cancer. This study will help us understand whether exercise can 

play a role in the rehabilitation of ovarian cancer survivors by 

alleviating persistent cancer-related symptoms and improving 

functional impairments and the ability to fully participate in life 

after cancer treatment.”

* Grant number: 5R01CA138556-04

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
Acupuncture Studied to Prevent 

Radiation-Induced Chronic Dry Mouth

division of cancer prevention

Xerostomia, or chronic severe dry mouth, is caused by 

reduced salivary flow and is a common side effect for 

many patients receiving radiotherapy for head and 

neck cancers. Most of the current treatments for xerostomia are 

palliative and offer limited benefit, but studies have begun to 

show promising results for the use of acupuncture in preventing 

and lessening xerostomia.

NCI has supported two small studies, conducted at the MD Anderson Cancer Center and the Fudan University Cancer Hospital 

in Shanghai, China, that investigated the feasibility and efficacy 

of acupuncture as a potential preventive therapy for radiation-induced chronic dry mouth. Based on promising results from the 

previous studies*, NCI is currently funding** two large, randomized, phase III trials that examine the effects of acupuncture for 

preventing or treating radiation-induced xerostomia.

Lorenzo Cohen, Ph.D., professor in the MD Anderson 

Departments of General Oncology and Behavioral Science and 

director of the cancer center’s Integrative Medicine Program, is 

the principal investigator of the grants, which have supported all 

of these acupuncture studies. He said the first phase III study, 

already well underway, is testing the use of acupuncture in 

preventing xerostomia in patients undergoing radiotherapy for 

head and neck cancer or nasopharyngeal carcinoma. 

According to Dr. Cohen, the clinical trial compares active 

acupuncture with the use of a placebo or “sham” version of 

acupuncture, as well as with a third group of patients who will 

receive usual medical care. Each of the three arms of the study 

will enroll 100 patients, divided evenly between MD Anderson 

and the Fudan Hospital.

Patients in the two acupuncture groups (active and sham) are 

treated 3 times weekly during the 7 weeks they receive radiation 

therapy. The comparison with sham acupuncture is important, 

Dr. Cohen explained, because some previous studies have found 

that “you often don’t see any clinical differences between the 

two approaches although both of them are usually better than 

usual care alone.” Both types of acupuncture treatments used 

in the study involve “combinations of real needles and sham 

needles (blunt needles that touch the skin then retract into their 

handles),” he explained. “This is something we’re not telling our 

patients in the study so that we can keep them ‘blinded’ about 

which acupuncture treatment they’re receiving.” 

The study is evaluating the patients’ self-reported outcomes based 

on a xerostomia questionnaire, which assesses severity of dry 

mouth symptoms and their interference with quality of life. In 

addition, Dr. Cohen and his colleagues are measuring saliva flow 

rates using standardized sialometry collection techniques. “We’ll 

also be looking at the constituents of the saliva, such as pH, 

buffering capacity, viscosity, and the different proteins that are in 

the saliva,” he noted. Patient assessments occur at baseline, midand immediately post- radiation treatment, as well as at 3, 6, and 

12 months following treatment.

The second major research study of acupuncture (active and 

sham) and xerostomia will start later in 2012 in over a dozen 

institutions around the United States that are part of the NCI’s 

Community Clinical Oncology Program (CCOP) network. The 

study will examine the effects of acupuncture to reduce the 

severity of radiation-induced xerostomia in patients with chronic 

xerostomia who have already completed radiotherapy for head 

and neck cancer.

“I’m hoping – if these two large, well-designed clinical 

trials confirm our earlier positive findings – that the use of 

acupuncture for the prevention and treatment of xerostomia will 

become the standard of care for this debilitating problem,” Dr. 

Cohen commented. He added that he hopes these studies will 

also clear the way for health insurance coverage of the treatment. 

However, he noted, if the studies show that active and sham 

acupuncture produce equivalent results and are both better 

than usual care, that will open up areas of additional research to 

determine the reasons for those similarities. 

* Meng, Z., Garcia, M. K., Hu, C., Chiang, J., Chambers, M., Rosenthal, D. I., & 

Cohen L. (2012). Randomized controlled trial of acupuncture for prevention of 

radiation-induced xerostomia among patients with nasopharyngeal carcinoma. 

Cancer, 118(13), 3337-44.

** Grant numbers: 5R01CA148707-02, 1R01CA160880-01A1

31

improv ing t he qua l i t y of l ife for c a ncer pat ien ts, surv i vors, a nd t heir fa mil ies
32

Exercise Study for Metastatic Breast Cancer 

Patients May Offer Benefits

division of cancer prevention

There is growing recognition and acceptance of the 

beneficial role of exercise following a breast cancer 

diagnosis. Studies have suggested that exercise improves 

symptom control and may be associated with reductions in 

cancer-related and overall death rates in women with breast 

cancer. NCI is currently supporting a pilot research study* in 

women with metastatic breast cancer (MBC) as a first step in 

determining the feasibility of launching large-scale clinical trials 

investigating the effects of exercise on breast cancer outcomes.

Lee Jones, Ph.D., Associate Professor and Scientific Director of 

the Duke University Center for Cancer Survivorship, who is the 

principal investigator of the study, commented, “There are a lot 

of research studies that look at the role of exercise in women with 

early stage breast cancer, but few studies have looked at the role of 

exercise in patients with metastatic disease.”

Jones and his team are conducting a randomized phase II clinical 

trial in women with MBC. Half of the patients will participate in a 

treadmill walking program, while the remainder of patients will be 

in a control group, doing only low-intensity stretching exercises. 

The study focuses on the safety and feasibility of exercise training 

as opposed to the potential role of exercise to improve disease 

outcomes in women with metastatic disease. Before addressing 

these types of questions, it is first of crucial importance to 

determine if exercising by these individuals is safe or possible 

“because MBC is a totally different clinical scenario than 

those with early-stage disease,” Dr. Jones noted. Women with 

MBC face many additional challenges from advanced disease 

and its treatments, including drug toxicities, infections, and 

hospitalizations, he added. “We have to be on our toes because 

their situations can change week-to-week.”

Dr. Jones reported they have enrolled about 30 women into the 

study so far and have identified two distinct groups of MBC 

patients. “There is a group who essentially do very well with 

exercise,” he said. “And then there is another group who really 

want to exercise but they’re just not able to because of toxicity, 

disease progression, and other factors. I believe this study is 

going to be extremely informative in terms of working out the 

characteristics of individuals with advanced disease who may be 

able to tolerate and benefit from an exercise program.”

“That is a simple question but it’s an important first step towards 

moving ahead with larger clinical trials to really get to some of 

the biology of what’s going on,” Dr. Jones continued. “It’s not 

just what can we do to help these patients feel better as they go 

through all these treatments, but can we also impact clinical and 

disease outcomes in these patients?”

If the pilot study shows promising results for exercise in MBC 

patients in terms of program adherence, adverse events, and 

safety profile, “that would bode well for future study in a more 

select population,” Dr. Jones noted. “I think exercise is definitely 

going to be complementary to standard care for these patients in 

the future.”

* Grant number: 5R21CA143254-02 

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
appendix

NCI-supported Clinical Trials in CAM Research

33
34

An NCI-supported clinical trial meets one or more of the following criteria: the protocol (1) has been reviewed and 

approved by NCI’s CTEP Protocol Review Committee or by an approved NCI-designated Cancer Center Protocol Review and 

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

Title Phase Type Status Age Sponsor Protocol IDs

Pediatric/Adolescent

Phase III Randomized Study 

of Glutamic Acid in Reducing 

Vincristine-Related Peripheral 

Neurotoxicity in Young Patients 

Undergoing Vincristine-Containing 

Treatment for Wilms’ Tumor, 

Rhabdomyosarcoma, Acute 

Lymphoblastic Leukemia, or NonHodgkin’s Lymphoma

Phase III Supportive care, 

Treatment

Active 3 to 20 NCI SCUSF-0402, HLMCC-0402, 

NCT00369564, ACCL 0731

Acupuncture Point Stimulation for 

Treatment of Chemotherapy Nausea 

and Vomiting

No phase 

specified

Supportive care Active 8 to 21 NCI, Other PEDSVAR0016, NCI-2011-

03653, NCT01492569

Pilot Study of Educational and 

Promotional Materials Development 

For Use In Promoting Physical 

Activity In Community-Based AfterSchool Programs By Multiethnic, 

Urban Adolescents

No phase 

specified

Educational/

Counseling/Training, 

Prevention

Active 11 to 14 NCI MSUHNS-0003669, 

FWA00005270, 

NCT00301158

Adult

Bladder

Green Tea Extract in Treating Patients 

With Nonmetastatic Bladder Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other CDR0000594276, WCCCUWI06-8-01, H2007-0250, 

07-1270-03, UWI06-8-01, 

CO06810, NCT00666562

Brain

Phase II Randomized Study of 

Adjuvant Boswellia serrata and 

Standard Treatment Versus Standard 

Treatment Alone in Patients With 

Newly Diagnosed or Recurrent HighGrade Gliomas

Phase II Treatment Active 18 and over NCI CASE-CCF-7348, CCF7348, NCT00243022, 

CASE1304200

Yoga Therapy in Treating Patients 

With Malignant Brain Tumors

No phase 

specified

Educational/

Counseling/

Training, 

Supportive care

Approvednot yet 

active

18 and over NCI, Other CCCWFU 98410, NCI-2010-

02044, NCT01234805

Breast

Diindolylmethane in Treating 

Patients With Breast Cancer

Phase III, 

Phase II

Biomarker/

Laboratory analysis, 

Diagnostic, 

Treatment

Active 19 and over NCI, Other 10-0366-04, NCI-2011-

00710, NCT01391689

Oral Curcumin for Radiation 

Dermatitis

Phase III, 

Phase II

Biomarker/

Laboratory analysis, 

Supportive care, 

Treatment

Active, not 

recruiting

21 and over NCI URCC 10054, URCC 09005, 

NCT01246973

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
35

a ppendi x: nci-support ed cl inic a l t r i a ls in c a m r ese a rch

Title Phase Type Status Age Sponsor Protocol IDs

Phase III Randomized Study of

Cranial Microcurrent Electrical 

Stimulation in Reducing 

Chemotherapy-Related Symptoms 

in Women With Stage I-IIIA 

Breast Cancer Receiving Adjuvant 

Chemotherapy

Phase III Biomarker/

Laboratory analysis, 

Supportive care

Active Adult NCI MCV-MCC-11995, MCC11995, NCT00902330

Phase III Randomized Study of 

Omega-3-Fatty Acid in Treating 

Aromatase Inhibitor-Induced 

Musculoskeletal Pain and Stiffness 

in Patients With Stage I, II, or IIIA 

Breast Cancer

Phase III Biomarker/

Laboratory analysis, 

Supportive care

Active Not 

specified

NCI SWOG-S0927, S0927, 

NCT01385137

Phase III Randomized Study 

of Acupuncture Versus Sham 

Acupuncture Versus Waiting List 

for Joint Symptoms Related to 

Aromatase Inhibitors in Patients 

With Stage I-III Breast Cancer

Phase III Biomarker/

Laboratory analysis, 

Supportive care

Approvednot yet 

active

PostmenopausalNCI SWOG-S1200, S1200, 

NCT01535066

Menopause and Meditation for 

Breast Cancer Survivors

Phase II, 

Phase I

Supportive care Active 30 to 70 NCI, Other 1R21CA106336-01A1, 

NCT00156416

Phase II Randomized Study of 

High-Dose Cholecalciferol in 

Premenopausal Women at High-Risk 

for Breast Cancer

Phase II Biomarker/

Laboratory analysis, 

Prevention

Active 18 to 50 NCI SWOG-S0812, S0812, 

NCT01097278

Broccoli Sprout Extract in 

Treating Women Who Have Had a 

Mammogram and Breast Biopsy

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 21 and over NCI, Other CDR0000634111, 

R21CA132236, 

P30CA069533, OHSU-4702, 

eIRB 4702, OHSU-LAY-01, 

NCT00843167

Alkaline Water in Reducing Skin 

Toxicity in Women With Breast 

Cancer Undergoing Radiation 

Therapy

Phase II Supportive care, 

Treatment

Active 18 and over NCI, Other CASE2109, NCI-2010-

01233, NCT01487954

Study of CoQ10 During One Cycle 

of Doxorubicin Treatment for Breast 

Cancer

Phase I Supportive care, 

Treatment

Active 21 and over NCI, Other AAAD8521, NCT00976131

Cook for Your Life No phase 

specified

Behavioral study, 

Biomarker/

Laboratory analysis, 

Educational/

Counseling/Training

Active 21 and over NCI, Other AAAE9701,

1R21CA152903-01, 

NCT01414062

Randomized Study of Vitamin D and 

Breast Cancer Biomarkers in Female 

Patients

No phase

specified

Biomarker/

Laboratory analysis, 

Prevention

Active 55 and 

under

NCI CALGB-70806, CALGB 

70806, NCT01224678

Soy Isoflavones Supplementation in 

Treating Women at High Risk For or 

With Breast Cancer

No phase 

specified

Diagnostic, 

Prevention, 

Treatment

Active 30 to 75 NCI, Other 1B-10-6, NCI-2010-01847, 

NCT01219075

Effects of Tibetan Yoga on Fatigue 

and Sleep in Cancer

No phase 

specified

Supportive care Active 18 and over NCI, Other 2005-0035, NCT00507923

Randomized Study of Magnesium 

Oxide in Postmenopausal Women 

With Hot Flashes and a History of 

Breast Cancer

No phase 

specified

Supportive care Active 18 and over NCI NCCTG-N10C2, N10C2, 

NCT01439945
36

Title Phase Type Status Age Sponsor Protocol IDs

Home-Based Symptom Management

Via Reflexology for Breast Cancer 

Patients

No phase 

specified

Supportive care Active 21 and over NCI, Other 1R01CA157459-01, 

NCT01582971

Randomized Study of Education With 

or Without Exercise and Counseling 

in Preventing Lymphedema in 

Women With Stage I-III Breast 

Cancer Who Are Undergoing Axillary 

Lymph Node Dissection

No phase 

specified

Supportive care, 

Treatment

Active 18 and over NCI CALGB-70305, CALGB 

70305, NCT00376597

Phase II Pilot Study of Magnesium 

Oxide in Treating Menopausal Hot 

Flashes in Women With Cancer

Phase II Supportive care Active 18 and over NCI MCV-MCC-12062, MCC12062, NCT01008904

Venlafaxine and Hypnosis or Focused 

Attention In Treating Patients With 

Hot Flashes

No phase 

specified

Supportive care Active 18 and over NCI, Other MC09C7, NCI-2009-01303, 

09-003233, NCT01000623

Acupressure for Persistent Cancer 

Related Fatigue

Phase III, 

Phase II

Supportive care Active 18 to 75 NCI, Other CA151445, NCT01281904

Cancer Survivors

Phase II Randomized Study of Green 

Tea Catechin Extract in Patients at 

High-Risk for Recurrent Colonic 

Neoplasia

Phase II Biomarker/

Laboratory analysis, 

Prevention

 Approvednot yet 

active

40 and over NCI MAYO-MC084C, MC084C, 

R01-CA-132991

Phase II Randomized Study of Two 

Home-Based Interventions for 

Sleep-Wake Disturbances in Cancer 

Survivors

Phase II Supportive care Active 18 and over NCI NCCTG-N07C4, N07C4, 

NCT00993928

Randomized Pilot Study of Hypnosis 

in Controlling Hot Flashes in Women 

Who are Breast Cancer Survivors

No phase 

specified

Supportive care Active Over 18 NCI S-WHITE-8165, 

NCT00094133

L-Arginine Supplements in Treating 

Women Who Are Cancer Survivors

No phase 

specified

Supportive care Active Adult NCI, Other CDR0000532277, 

CCCWFU-05-04-01, 

CCCWFU-97106, WFU 05-

04-01, NCT00459134

Cervix

Folic Acid Clinical Trial for the 

Prevention of Cervical Cancer 

Phase II Biomarker/

Laboratory analysis, 

Prevention

 Active 19 and over NCI UAB-F060511015, 

F060511015, UABIRB0000196, NCT00703196

Mindfulness-Based Stress Reduction 

or General Health Education in 

Improving Immune Response to 

Human Papilloma Virus in Patients 

With Cervical Dysplasia

No phase 

specified

Behavioral study, 

Biomarker/

Laboratory analysis, 

Educational/

Counseling/Training

 Active 18 and over NCI FCCC-06851, 06-851,

NCT00653146

Randomized Study of Magnetic 

Acupressure in Reducing Pain in 

Cancer Patients Undergoing Bone 

Marrow Aspiration and Biopsy 

No phase 

specified

Diagnostic, 

Supportive care

 Active 18 and over NCI JHOC-J07103, J07103, 

JHOC-NA_00013389, 

NCT00670917

Colon/Rectum

Phase III Study of the Effect of 

Vitamin E and/or Selenium on 

Adenomatous Colorectal Polyps 

in Men Enrolled on SELECT Trial 

SWOG-S0000

Phase III Natural history/

Epidemiology, 

Prevention

Active 50 and over NCI SWOG-S0000D, S0000D, 

NCT00706121

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
37

a ppendi x: nci-support ed cl inic a l t r i a ls in c a m r ese a rch

Title Phase Type Status Age Sponsor Protocol IDs

Selenium for Prevention of

Adenomatous Colorectal Polyps

Phase III Prevention Active 40 to 80 NCI, Other CDR0000353185, 

P30CA023074, 

UARIZ-00-0430-01, UARIZHSC-00142, P01CA041108, 

00-0430-01, NCT00078897

Cholecalciferol(25-[OH]-Vitamin D) 

in Treating Patients With Colorectal 

Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other CASE2210, NCI-2011-

01280, NCT01403103

Polyphenon E in Treating Patients 

With High-Risk of Colorectal Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Approvednot yet 

active

40 and over NCI, Other MC084C, NCI-2012-00058, 

NCT01606124

Phase II Randomized Study 

of Acupuncture in Reducing 

Postoperative Ileus in Patients Who 

Have Undergone Segmental or 

Subtotal Colectomy for Colorectal 

Cancer

Phase II Supportive care Active Over 18 NCI MSKCC-06145, 

NCT00425412

Phase I/II Randomized Study 

of Inositol for the Prevention of 

Colorectal Cancer in Patients With 

Colitis-Associated Dysplasia 

Phase I Biomarker/

Laboratory analysis, 

Prevention

Active 18 and over NCI NU-NWU09-13-02, NWU09-

13-02, NCT01111292

Vitamin E Supplements in Treating 

Patients Undergoing Surgery for 

Colorectal Cancer

Phase I Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other 120901, CDR0000642446, 

IRB#0220090065, CINJ120901, NCT00905918

Doctor-Recommended Home-Based 

Exercise Program or Relaxation 

Training in Improving Physical 

Functioning and Controlling 

Symptoms in Patients With Stage 

IV or Recurrent Colon Cancer That 

Cannot Be Removed By Surgery

No phase 

specified

Behavioral study, 

Supportive care

Active 18 and over NCI MDA-2009-0288, 2009-

0288, NCT00985400

Head/Neck

Phase III Randomized Study of 

Lactobacillus brevis CD2 Lozenges 

Versus Placebo in the Prevention 

of Acute Oral Mucositis in Patients 

With Squamous Cell Carcinoma 

of the Head and Neck Receiving 

Concurrent Radiotherapy and 

Chemotherapy

Phase III Biomarker/

Laboratory analysis, 

Supportive care, 

Treatment

Approvednot yet 

active

18 and over NCI NCCTG-N11C5, N11C5, 

NCT01545687

Acupuncture in Treating Dry Mouth 

Caused By Radiation Therapy in 

Patients with Head and Neck Cancer 

Phase III Supportive care Approvednot yet 

active

Not 

specified

NCI MDA-04-01, MDA-04-01, 

MDA 04-01, NCT01141231

Xerostomia Acupuncture Trial Phase III Supportive care Active 18 and over NCI, Other 2010-0584, NCT01266044

Phase II Randomized 

Chemoprevention Study of BowmanBirk Inhibitor Concentrate in Patients 

With Oral Leukoplakia

Phase II Biomarker/

Laboratory analysis, 

Prevention, Treatment

Active 18 and over NCI UCIRVINE-UCI-98-34, 

UCIRVINE-UCI-1998-521, 

NCT00330382, U01-

CA-72294

Curcumin Biomarker Trial in Head 

and Neck Cancer

No phase 

specified

Biomarker/

Laboratory analysis, 

Treatment

Active 18 to 90 NCI, Other H08-081, 1R21CA137545-

01A2, FWCC, NCT01160302
38

Title Phase Type Status Age Sponsor Protocol IDs

Lung

Exercise and Lung Cancer Trial Phase III Behavioral study Active 21 to 80 NCI, Other 00018255, 1R01CA138624-

01A1, NCT01068210

Phase II Randomized Study of 

Inositol for the Prevention of Lung 

Cancer in Current or Former Smokers 

With Bronchial Dysplasia

Phase II Biomarker/

Laboratory analysis, 

Prevention

Active 45 to 79 NCI MAYO-MAY06-8-01, 

MAY06-8-01, NCT00783705

Calcitriol in Preventing Lung Cancer 

in Smokers and Former Smokers at 

High Risk of Lung Cancer

Phase I Biomarker/

Laboratory analysis, 

Prevention

Active 40 to 79 NCI, Other CDR0000596506, 

P30CA016056, 

RPCI-I-90206, I 90205, 

NCT00690924

Oleandrin (Nerium Oleander Extract) 

in Combination With Carboplatin and 

Docetaxel in Patients With Advanced 

Non-Small Cell Lung Cancer

Phase I Biomarker/

Laboratory analysis, 

Supportive care

Approvednot yet 

active

18 and over NCI MDA-2011-0147, 2011-

0147, NCT01562301

Flaxseed Supplementation in 

Patients With Locally Advanced 

or Metastatic Non-Small Cell 

Lung Cancer Undergoing 

Chemoradiotherapy and Radiation 

Therapy

Phase I Biomarker/

Laboratory analysis, 

Treatment

 Active 18 and over NCI UPCC-03309, UPCC 

03309, IRB# 806733, 

NCT00955942

Multiple

Phase III Randomized Study of Live 

Freeze-dried Lactic Acid Bacteria 

Probiotic (VSL#3®) Versus Placebo 

in the Prevention of Acute Enteritis 

in Patients With Cancer Receiving 

Concurrent Chemotherapy and Pelvic 

Radiation Therapy

Phase III Supportive care, 

Treatment

Approvednot yet 

active

18 and over NCI NCCTG-N10CB, N10CB, 

NCT01473290

Probiotic Supplementation in 

Preventing Treatment-Related 

Diarrhea in Patients With Cancer 

Undergoing Chemotherapy

Phase II Biomarker/

Laboratory analysis, 

Supportive care

Approvednot yet 

active

18 and over NCI, Other VAR0084, NCI-2012-01127, 

NCT01644097

Yoga-Based Cancer Rehabilitation 

Program

No phase 

specified

Behavioral study, 

Supportive care

Active 18 and over NCI, Other #2000-007, NCI 

R03 CA88598-01A1, 

NCT00179348

Mindfulness Relaxation Compared 

With Relaxing Music and Standard 

Symptom Management Education 

in Treating Patients Who Are 

Undergoing Chemotherapy for Newly 

Diagnosed Solid Tumors

No phase 

specified

Educational/

Counseling/

Training, 

Supportive care

Active 18 and over NCI MDA-CCC-0106, MDACCC-01-06, 2004-0024, 

NCT00086762

Healing Touch or Guided Imagery 

In Treating Pain, Fatigue, Nausea, 

and Anxiety in Patients Undergoing 

Chemotherapy

No phase 

specified

Supportive care Active 18 and over NCI, Other CCCWFU 97511, NCI-2012-

00164, NCT01553578

No Specific Cancer Type/Healthy Volunteer

Phase III Randomized Study of a 

Psychoeducation, Paced Respiration, 

and Relaxation Intervention for 

Caregivers of Patients Undergoing 

Bone Marrow Transplantation

Phase III Biomarker/

Laboratory analysis,

Educational/

Counseling/Training, 

Supportive care

Active 18 and over NCI UCHSC-080303, 08-0303, 

NCT00833898

Vitamin D and Omega-3 Trial (VITAL) Phase III Prevention Active 60 and over NCI, Other 2009P-001217,

NCT01169259

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011
39

a ppendi x: nci-support ed cl inic a l t r i a ls in c a m r ese a rch

Title Phase Type Status Age Sponsor Protocol IDs

Exercise or Relaxation for Smoking

Cessation

No phase 

specified

Behavioral study Active 50 and over NCI, Other 09-097-2, 1RO1 DA024872-

01A1, NCT00921388

Patient-Directed Lifestyle Change and 

Health Promotion Program or Usual 

Care in Low-Income, Uninsured 

Participants in Los Angeles County, 

California

No phase 

specified

Behavioral study, 

Educational/

Counseling/Training, 

Health services 

research

Active 18 and over NCI, Other CDR0000561559, UCLA-G060801501A, G06-08-015-

01, NCT00521209

Randomized Study of Lycopene 

in Preventing Prostate Cancer in 

Healthy Participants

No phase 

specified

Biomarker/

Laboratory analysis, 

Prevention

Active 18 and over NCI UIC-2004-0217, 

NCT00322114

Studying the Effect of Freeze-Dried 

Table Grape Powder on Blood 

Estrogen Levels in Postmenopausal 

Women

No phase 

specified

Biomarker/

Laboratory analysis, 

Prevention

Active 18 and over NCI, Other CDR0000581219, 

P30CA015083, MC0536, 

06-002061, MAYO-MC0536, 

NCT00611104

Cruciferous Vegetable Intake 

and Histone Status in Screening 

Colonoscopy Patients

No phase 

specified

Biomarker/

Laboratory analysis, 

Prevention, Screening

Active 50 to 75 NCI, Other P01 CA090890, 

NCT01344330

Spiritual Care in Improving Quality 

of Life of Patients, Caregivers, and 

Hospital Staff

No phase 

specified

Supportive care Active 18 and over NCI, Other 11110, NCI-2011-02730, 

NCT01432431

Pancreas

Vitamin E d-Tocotrienol Administered 

to Subjects With Resectable 

Pancreatic Exocrine Neoplasia

Phase I Treatment Active 18 and over NCI, Other MCC-15630, 

1R01CA129227-01A1, 

NCT00985777

Prostate

Phase II/III Randomized Study of 

Adjuvant Soy Protein Isolate in 

Preventing Recurrence in Patients 

Who Have Undergone Radical 

Prostatectomy for Stage II Prostate 

Cancer

Phase III, 

Phase II

Biomarker/

Laboratory analysis, 

Treatment

Active 40 to 75 NCI UIC-2006-0706, 2006-0706, 

NCT00765479

Selenium in Preventing Prostate 

Cancer

Phase III Biomarker/

Laboratory analysis, 

Prevention

Approvednot yet 

active

Under 80 NCI, Other CDR0000654651, 

R01CA077789, 

P30CA023074,

UARIZ-99-0045-01, 99-

0045-01, NCT00978718

Improving Continence and Quality of 

Life in Prostate Cancer Patients

Phase III Health services

research, 

Supportive care

Active 21 and over NCI, Other 1R01CA127493-01A2, 

NCT01365182

Effects of Tomato-Soy Juice on 

Biomarkers in Patients With Prostate 

Cancer Undergoing Prostatectomy

Phase II, 

Phase I

Biomarker/

Laboratory analysis, 

Treatment

Active Any age NCI, Other CDR0000642377, OSU2007C0026, 2007C0026, 

NCT01009736

Vitamin D and Soy Supplements 

in Treating Patients With Recurrent 

Prostate Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active Over 18 NCI, Other CDR0000554969, 

P30CA012197, 

CCCWFU-85106, 

CCCWFU-IRB00000371, 

NCT00499408

Green Tea or Water in Treating 

Patients With Prostate Cancer 

Undergoing Surgery

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 40 to 75 NCI, Other CDR0000596162, 

R01CA116242, 

P30CA016042, UCLA061109702, 06-11-097-02, 

NCT00685516
40

Title Phase Type Status Age Sponsor Protocol IDs

Selenium in Treating Patients With 

Prostate Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active Under 85 NCI, Other CDR0000614471, 

R01CA079080, 

P30CA023074, 

UARIZ-97-0395, UARIZHSC-97-57, DAMD17-98-1-

8580, 97-0395-01, Watchful 

Waiting, NCT00752739

Diindolylmethane in Treating 

Patients With Stage I or Stage II 

Prostate Cancer Undergoing Radical 

Prostatectomy

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other CDR0000641168, 

P30CA022453, WSU2007-128, 2007-128, 

NCT00888654

Genistein in Treating Patients With 

Prostate Cancer

Phase II Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other NCI 09U2, NCI-2010-

00941, STU00019487, 

P50CA090386, 

NCT01126879

Study of Polyphenon E in Men With 

High-grade Prostatic Intraepithelial 

Neoplasia

Phase II Prevention Active 30 to 80 NCI, Other MCC-15008, R01 CA12060-

01A1, NCT00596011

L-Arginine Supplementation With 

or Without Enzyme Inhibitors In 

Treating Erectile Function and 

Quality of Life of Prostate Cancer 

Survivors Previously Treated With 

Radiation Therapy

Phase II Supportive care Active 18 and over NCI, Other cccwfu 98110, WFU-08-08-

09, NCT01105130

Chemoprevention of Prostate 

Cancer, HDAC Inhibition and DNA 

Methylation

No phase 

specified

Biomarker/

Laboratory analysis, 

Prevention

Active 21 and over NCI Portland VA-09-0607, 2096, 

6232, NCT01265953

Polyunsaturated Fatty Acids in 

Treating Patients With Prostate 

Cancer Undergoing Prostate Biopsy 

and/or Surgery

No phase 

specified

Biomarker/

Laboratory analysis, 

Treatment

Active 18 and over NCI, Other CDR0000538993, 

DFCI-03116, 03-116, 

NCT00458549

Skin

Pilot Trial to Evaluate the Effect of 

Vitamin D on Melanocyte Biomarkers

No phase 

specified

Biomarker/

Laboratory analysis, 

Prevention

Approvednot yet 

active

18 to 75 NCI, Other SKIN0010, SU-10272011-

8570, NCT01477463

a nnua l r eport on compl emen ta ry a nd a lt er nat i v e medicine f y 2011

Released March 2013

NIH... Turning Discovery Into Health®