development of taxol and clinical investigations of taxol in combination with other drugs will continue in 1992. Studies in Prevention is the most effective way to eliminate a disease. chemoprevention point the way to the day when people at high risk for cancer or those with premalignant conditions will be protected from getting cancer by adding a vitamin supplement, a micronutrient or other chemopreventive agent to their diets. Recently, findings from chemoprevention studies have shown that vitamin A-related compounds can prevent oral cancers and second primary head and neck tumors. A new prevention clinical trial will employ tamoxifen, an anti-estrogen agent, as a breast cancer prevention agent. Tamoxifen has the potential to reduce the incidence of breast cancer by some 30 to 50 percent among postmenopausal women. NCI is planning a two to three year study to determine the feasibility of conducting a full randomized dietary intervention trial to assess the impact of a low fat diet on the prevention of cancer and cardiovascular disease among women. A broad cross-section of women will be recruited to the feasibility trial with special attention to women from poor and underserved minority groups whose cancer mortality statistics are particularly high. Tobacco use remains the single most deadly contributor to cancer mortality rates. NCI supports several large-scale smoking cessation studies: the Community Intervention Trial for Smoking Cessation (COMMIT) and the American Stop Smoking Intervention Study (ASSIST). There is an intense effort to develop vaccines and vaccine-like approaches to the prevention of cancer. Vaccination is a classical tool to prevent diseases caused by a virus, and since a number of cancers are linked to a virus, vaccination is a promising strategy. For instance, Epstein-Barr virus and related viruses are detected in Burkitt's and other B cell lymphomas, oral hairy leukoplakia, nasopharyngeal carcinoma, and AIDS-related lymphomas. Vaccination is already preventing infection by the hepatitis B virus, a risk factor for the development of liver cancer. NCI-supported researchers have reported significant regressions of non-virus-caused malignant melanoma tumors using a vaccine-like approach to increase the patient's immune response. NCI has pioneered the rapid communication about advances in clinical research. professional journals, PDQ, clinical announcements, press conferences, and consensus development conferences. The latest information about cancer treatment and clinical trials is available via the NCI's Cancer Information Service. Over 500,000 patients, families and doctors received information via the CIS toll-free 1-800-4-CANCER telephone number. NCI also reaches the public in novel ways, for instance, adding cancer education messages to rental videos of popular films. Last year, to extend information services abroad, NCI installed a state-of-the-art system using a compact disk technology (CDROM) product at demonstration sites in three cancer research institutes in Eastern Europe. In 1992, an additional 15 systems will be installed in developing countries. A number of NCI publications also are being provided free of charge to key medical libraries and academic institutions in Poland, Hungary, and the Soviet Union. In conclusion, we have accrued understanding of the basic biology of cancer, which in turn is pointing to effective prevention, diagnostic and treatment strategies. We must continue our progress and NCI stands ready to fulfill that goal. Mr. Chairman, the FY 1992 budget request for the National Cancer Institute is $1,810,230,000. I will be happy to answer any questions. BIOGRAPHICAL SKETCH OF DR. SAMUEL BRODER PERSONAL: b. February 24, 1945; US citizenship Married, two children EDUCATION: University of Michigan, Ann Arbor, MI College of Literature, Science and the Arts (high honors) National Cancer Institute, National Institutes of Health, Bethesda, MD BOARD CERTIFICATIONS and LICENSES: 1973 Certified in Internal Medicine Licensed to practice Medicine in California and Maryland HONORS: Phi Beta Kappa Alpha Omega Alpha Fellow of the Life Insurance Medical Research Fund Upjohn Achievement Award Arthur S. Flemming Award Public Health Service/Meritorious Service Medal Fourth Biennial Chemistry as a Life Science Lectureship/Rutgers University Alpha Omega Alpha Distinguished Professor/Dartmouth Medical School Robert T. Wong, M.D. Endowment Award/University of Hawaii Foundation Samuel Rudin Award/Columbia Presbyterian Hospital First Annual Award for Outstanding Achievement in International Health Harvey W. Wiley Medal/FDA Commissioner's Special Citation Health Leader of the Year Award/Commissioned Officers Association, 1990 Dr. Frederick Stohlman Lecture Award/Volga Wilsede Meeting Lifetime Science Award/Institute for Advanced Studies in Immunology & Aging GENE THERAPY Senator HARKIN. Thank you very much, Dr. Broder. The first thing that caught my attention was the gene therapy experiment that was done last fall on a little girl with a previously incurable disease that shuts down the immune system. I was going to ask you about that, but you tell me that at this point it looks as though it has been successful. Dr. BRODER. This is an important collaboration between the Cancer Institute and my distinguished colleague's Institute, Dr. Lenfant, the Heart, Lung, and Blood Institute. It represents the work of Dr. French Anderson, Dr. Michael Blaese, Dr. Steve Rosenberg, with active participation of a very important scientist from your State, sir, Dr. Culver. We feel that while this is preliminary and should not be taken to mean that we now have a standard, conventional treatment for this unusual immunodeficiency, our scientists are convinced that there has been, in fact, a real improvement in this child's immune function, and at least from an experimental point of view, we consider this aspect of the experiment to have made successful progress. We are not ready to say we now have conventional curative therapy for this unusual form of a disease, and we should use some caution as to how to extrapolate these findings. Senator HARKIN. Has her immune system returned to normal? Dr. BRODER. It has not returned to normal, but we do have evidence of an improvement in what are called lymphocyte functions and her ability to recognize foreign substances, so-called antigens, that might be thought of as invaders of her body. She is making a response to certain types of antigens that she would not normally have made. Senator HARKIN. How much longer will she be undergoing this therapy? Dr. BRODER. Well, this is viewed as a case-by-case thing. We do not have any background. There is no textbook we can look at. This is the first patient on Earth who has received this particular approach. And to be candid with you, I would have to say that from our point of view we are learning as we go along, I do not think it would be appropriate for me to tell you that we know the precise schedule. But if she continues to be successfully treated, we will certainly continue the procedures as long as we think she is benefiting from them. But this is a first case, and it is very difficult to make an extrapolation. A second child has been treated and it is too early for us to say at this point whether there is progress or not. Senator HARKIN. The same immunodeficiency? Dr. BRODER. The same immunodeficiency. And two patients with cancer, as I mentioned, have been treated using related technology, but for a different purpose. Again, in that setting, it is too soon for us to say whether this approach is adding to the overall benefit of the patient. But it is no longer possible to say we will at some future time enter into the world of gene therapy for this purpose. We have already entered that world. UNCONVENTIONAL TREATMENTS Senator HARKIN. I do not know if you want to add anything to what Dr. Raub had said earlier in my question about the nonconventional things. You met also with Congressman Bedell. Dr. BRODER. Sir, I would like to say that I think it is very important for a variety of reasons for the National Cancer Institute to remain open to new ideas and to create a specific bond of trust with the public that it is open to new ideas and that all ideas compete on a level playing field. In that context, perhaps I could say that we have responded to an Office of Technology Assessment report that you touched on. We have made certain suggestions for increasing lines of communication, and we have an internal program in our organization-a cancer therapy evaluation program that is receptive to hearing new ideas and that will pursue new ideas. I would say that on three occasions in my recent memory we have followed up on what are called unconventional ideas. For example, laetrile was an unconventional idea, and we actually did an NCI funded clinical trial with laetrile. There was a great deal of controversy over a drug called hydrazine, and we, in fact, are doing a study with hydrazine to answer some questions. And we will ask our scientists to participate. NCI funding instruments will help do those studies. And finally, there was a randomized study, an appropriate control study, using vitamin C which was quite controversial at the time. I would say the latter, the vitamin C study, has considerable scientific implications, and, in fact, we are integrating vitamin C and related vitamins, small micronutrients, in a chemoprevention program both in the United States and abroad. We have a very large scale program in the United States and in China, and we feel that it is quite likely that some aspects of vitamin C or ascorbic acid and other related vitamins are likely to have biologically important activities in the world of chemoprevention, that is, preventing cancer before it occurs. We do not have all the data on that point. But the reason for me to give you this background is to signal you our understanding of your concerns. We know where you are coming from. We understand your concerns, and we try to remain open to new ideas. I would say that every major advance in cancer that we accept as conventional treatment today at one time was somebody's outlying idea, was some crazy person's idea, until it was accepted in the mainstream. And so, that would be true for chemotherapy, radiation therapy, and so on. These were all outside the mainstream. They were unconventional in their era. VITAMINS AND CHEMOPREVENTION Senator HARKIN. I appreciate that very much, Dr. Broder. I just jotted down that when you mentioned prevention, you said that vitamin derivatives have some indication of being a preventative measure. You just said that again. Dr. BRODER. That is correct. Senator HARKIN. You have some ongoing studies. Dr. BRODER. Yes, sir. We have a very strong commitment to what is called chemoprevention, and that means using micronutrients, sometimes vitamins, sometimes natural substances, sometimes certain hormones that are related to hormones in the body not necessarily for the purpose of treating cancer, but to prevent cancer. It is my personal view that prevention should be our highest priority. Prevention of a disease is always better and more cost-effective than attempting to treat a disease once it has occurred. An ounce of prevention in today's dollars is probably worth a kilogram of cure. And I feel that we have made progress in this area. We have certain vitamin A derivatives, which are included in the broad family of retinoids and substances such as beta carotene. These are related to the vitamins that one might have in the body. They definitely have been shown to be active-this is not speculative, they have been shown to prevent certain types of cancers. For example, we have some progress in preventing the development of second head and neck cancers in individuals who are at risk because they already have a first cancer of the head and neck. And we have been able to show that in some cases you can prevent a second disease. The whole area of chemoprevention is very exciting because there is an economy of scale involved. Almost anything that we could traditionally talk about that benefits cancer prevention-almost anything-would seriously augment our ability to prevent heart disease and other things, and so there is an economy of purpose here. I haven't discussed this specifically with Dr. Lenfant, but my instinct is that he would support that. WOMEN'S HEALTH: DIETARY FAT AND CANCER Senator HARKIN. Last, speaking about prevention and throwing in a little controversy here, obviously you know I am very strong |