NATIONAL CANCER INSTITUTE STATEMENT OF DR. SAMUEL BRODER, DIRECTOR BUDGET REQUEST Senator HARKIN. We now want to call up our panels. We will start first the panel with Dr. Samuel Broder, Director of the National Cancer Institute; Dr. Claude Lenfant, Director of the Heart, Lung, and Blood Institute; Dr. Harald Löe, Director of the National Institute of Dental Research; Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, and Associate Director for HIV Research at NIH. And we will go in the order in which I called, and not necessarily in any order of importance or priority, but this is the way my book is organized. So we will start with the National Cancer Institute. Dr. Broder, we are glad to have you with us this morning. Your budget request is for $1.694 billion, an increase of almost $60 million over last year, and a growth rate of approximately 3.7 percent. I also notice you intend to continue support for the 56 research centers, and your total number of research grants would be 3,109, a reduction of 10 grants from 1990. Dr. Broder, if you would proceed with a brief statement, and then what we will do is we will take each Institute and then we will come back for general questioning for everyone. PREPARED STATEMENT Your statements will all be made a part of the record in their entirety. I read them over the weekend and I would just ask you to please proceed and either summarize or highlight what you want us to focus on. [The statement follows:] (713) STATEMENT OF DR. SAMUEL BRODER One million Americans will learn this year that they have cancer and about half of them will eventually die of cancer. Our best response to the challenge of cancer a disease which causes suffering beyond metaphor -must be an intense effort to generate knowledge and to apply it quickly. The three foundation stones of the NCI are: basic research, clinical trials in prevention and therapy, and the cancer centers. The results of NCI's research belong to all Americans regardless of their race, age, income, social status, or place of residence. Cancer research and technology transfer require creative, highly trained scientists and clinicians and well equipped laboratories. Other resources are needed, such as a network of cancer centers, each bringing interdisciplinary approaches to cancer in its community, as well as addressing national and regional problems. An array of organized clinical trials is needed to generate knowledge regarding new drugs, preventions, and therapies. A vigorous program of clinical trials must involve academic centers and community physicians. Among other achievements, two NCI scientists (together with a colleague from the National Heart, Lung, and Blood Institute) made medical history last Spring by inserting new genetic material into human cells, returning the cells back to the patient, and then tracking the gene-engineered cells in the patient's circulatory system two months later. These experiments will lead to gene therapies and are based upon NCI basic research accomplishments. Recently, NCI-supported scientists have made a number of important molecular discoveries, including: the location of molecular abnormalities believed to contribute to lung, colon and breast cancer by a loss of a critical regulatory mechanism; the location of the gene responsible for familial malignant melanoma on; identification of five proteins, implicated in the process of metastasis (the wild spread of cancer). Such discoveries pave the way for future research on prevention and cure of cancer. For over 50 years, scientists have sought the cause of cystic fibrosis, and recently NCI-supported scientists discovered that the cystic fibrosis gene was linked to an oncogene (called met) thus providing a marker, which greatly facilitated the recent discovery and cloning of the cystic fibrosis gene. NCI-supported clinical trials have shown that in some cancers, adjuvant treatment after surgery can reach remaining microscopic tumors, prevent tumor recurrence, and prolong or save lives. Last year adjuvant treatment using a combination of levamisole and 5-Fluorouracil, after surgery in Dukes' C colon cancer, an advanced cancer, made an improvement in 5-year survival rate, reducing deaths by a third. There will be approximately 110,000 new cases of colon cancer in 1990, of which 21,000 will be classed as Dukes' C stage. Neoadjuvant therapy, that is using chemotherapy or radiotherapy before surgery, may shrink certain cancers and make it possible to limit surgery, permitting the salvage of structures like the bladder, rectum or breast which would otherwise have been sacrificed to stop the cancer. Clinical trials often take years to complete. Now, in addition to large clinical cooperative groups, NCI is using the mass media to draw attention to clinical trials. Accelerated enrollment speeds evaluation of new therapies and brings state-of-the-art therapies to more people. NCI has a long commitment to cancer prevention. Chemoprevention studies are being carried out in breast, lung, colon, bladder, and skin cancers with agents related to the retinoids, beta-carotene, vitamin E, selenium, and other substances. A recent study showed that a high wheat fiber diet decreased the number of large bowel polyps cancer precursors. This study was conducted in patients at high risk for large bowel cancer, but this diet may reduce the risk of bowel cancer among all Americans. - Sometimes research affects us right in our own backyards; NCI-supported scientists have studied and identified the mutagenic substances formed when meat is grilled or fried. These substances may contribute to a risk for NCI is studying a interventions with people already at high risk. One study is testing the effect of beta-carotene and retinol for asbestos workers who are at high risk for lung cancer. Another study is evaluating the effect of dietary fiber combined with calcium in individuals who have a high risk of colon cancer. NCI conducts national programs to educate the public about cancer, at times using innovative approaches such as working with supermarkets in minority neighborhoods to highlight food choices that may help to reduce the risk of cancer. NCI makes state-of-the-art information available to everyone in the country through the Cancer Information Service (CIS) via its toll-free 1-800-4-CANCER number. Over 500,000 people called CIS last year. Counselors use NCI's computerized Physician Data Query (PDQ), which describes state-ofthe-art cancer treatment and available clinical trials. This CIS is now reaching more states and more people than ever before. For white Americans under 65 the death rate for certain cancers is falling. But again this year, NCI statistics show that minority groups, the poor, the underserved and those over 65, have disproportionately high rates of cancer mortality. The reasons are complex and relate in part to special problems in terms of access to state-of-the-art prevention, early detection, and treatment. In response, NCI has made reduction of cancer mortality in these populations a high priority. NCI is publishing a new atlas of cancer mortality in nonwhite populations which shows geographic areas with high rates of cancer and this will guide epidemiologic studies and programs aimed at reduction of cancer in underserved groups. Also to this end, NCI has incorporated the National Black Leadership Initiative on Cancer which assists black community-based and national leaders in organizing programs for early detection and prevention of cancer. Lifestyle changes, compliance with screening guidelines and smoking cessation, can prevent cancer deaths. Consequently, lung cancer deaths for men in some age groups are declining slowly, but surely. Lung cancer accounts for 30 percent of cancer deaths, so any reductions will make a marked impact on cancer mortality in the future. Unfortunately, we need to do more to reach women and adolescents. Early detection of cancer saves lives and is not used to full advantage. The Pap test is widely available, yet 6,000 women die each year of cervical cancer. NCI has improved screening for cervical cancer and is working to increase its use. Breast cancer is one of the leading causes of cancer death in women with 150,000 new cases and 44,000 deaths in the United States expected in 1990 deaths that could be reduced by 30 percent or more if mammography guidelines were followed. - Last Fall, a Women's Leadership Summit on Mammography was held on Capitol Hill to launch NCI's National Breast Screening Awareness Campaign in an effort to reduce breast cancer deaths, by expanding mammography utilization. Where early detection or state-of-the-art treatment programs have been established, beneficial results are seen. A report from the San Francisco/ Oakland based Surveillance Epidemiology and End Result Program shows striking changes in early breast cancer detection and a dramatic shift towards less radical surgical treatment. Treatment research brings hope to today's cancer patient. New treatments are developed through clinical trials and where early results are promising, special interim Food and Drug Administration classifications such as the Group C mechanism allow private physicians to use the drugs for appropriate patients. This is extremely important because for some cancers experimental drugs are the only effective treatment available. The following drugs were placed in Group C status last year: levamisole plus 5-fluorouracil for adjuvant treatment of Dukes' C colon cancers; deoxycoformycin for the treatment of hairy cell leukemia refractory to the standard treatment of alpha interferon; and fludarabine phosphate for refractory chronic lymphocytic leukemia which represents a significant advance in this common kind of leukemia in adults, with about 9,600 new cases each year. Compounds developed at NCI and recently given New Drug Approval (prescription) status include: ifosfamide, flutamide, and carboplatin for treatment of the metastatic stage of testicular, prostatic, and ovarian cancer respectively. A New Drug Approval application for fludarabine for chronic lymphocytic leukemia has been made. NCI's research is helping to prolong survival by improving management of drug resistance which can render certain cancers impervious to chemotherapy. Agents being studied to combat drug resistance include: steroids and steroid antagonists, calcium channel blockers, cardiac antiarrhythmic drugs, immunosuppressants and monoclonal antibodies. Researchers have found that adding the drug verapamil, a calcium channel blocker used in cardiology, to the usual chemotherapy regimen reduced drug resistance in patients with refractory myeloma and non-Hodgkin's lymphoma. An old drug, suramin, long used for treating parasitic infections, is the first drug to have been found active in treating advanced prostate cancer, which has failed conventional. Clinical trials on breast cancer are comparing the effectiveness of tamoxifen, with and without radiation therapy, in women whose cancer has not spread to nearby underarm lymph nodes. Over 2,600 women will participate, but nearly 70,000 women have similar cancers. A study on small cell lung cancer is comparing standard treatment (chemotherapy and a daily dose of radiation) with an experimental regimen which uses the same chemotherapy, but with smaller, more frequent doses of radiation. About 360 people will be enrolled in this study over two years, but approximately 80,000 Americans would qualify by these criteria. A number of clinical trials are testing natural human biological substances as novel treatments. Colony stimulating factors (CSF) which originate in the bone marrow, are proving useful in some hard-to-treat childhood cancers, such as neuroblastoma and aggressive lymphoma. These factors are improving statistics for treating other cancers, e.g., breast cancer. The CSFs appear to protect the bone marrow (the site of production of blood components) during high-intensity chemotherapy. Although not the lead NIH agency, NCI has an important role in AIDS drug and vaccine development and NCI scientists continue to investigate the pathogenesis of AIDS, the biologic mechanisms by which the HIV causes infection, immune system destruction, multi-organ system dysfunction and some specific HIV-related cancers. The NCI intramural program has emerged as one of the most important centers in the world for development of therapeutics for children with AIDS. Last year, 16 new anti-viral drugs have moved into preclinical testing. Compounds are evaluated for activity against HIV on a high-capacity screen of cells. Since 1987, over 14,000 chemical structures have been tested, of which 70 had anti-HIV activity. It is expected that up to 100 anti-HIV compounds may be identified each year with only three to four compounds developed each year. In addition, NCI continues several AIDS epidemiologic and natural history studies, both descriptive and interventional, in the United States and abroad. This research has had encouraging results. An individual diagnosed with AIDS in 1982 had only a 30 percent chance of being alive 18 months after diagnosis. This situation improved first at the end of 1986 and then dramatically in 1987. AZT, a drug developed by NCI in collaboration with a private sector company, was approved by the FDA in March of 1987. Thus, an individual diagnosed in 1987 had a greater than 60 percent chance of being alive at 18 months. All of us are aware of the challenge and difficulties that we face. Progress against the suffering and deaths from cancer will not be easy, but we have built a program where success is possible and the continued support evidenced by the President's Budget ensures that it will occur. Mr. Chairman, the 1991 budget request for the NCI totals $1,694,059,000. I would be pleased to answer any questions. 1970-1971 1971-1972 1975-1976 1976-1981 1981-1988 1989-pres Internship (Medicine), Stanford University, Palo Alto, CA Institute, National Institutes of Health, Bethesda, MD Senior Investigator, Metabolism Branch, National Cancer Director, National Cancer Institute, National Institutes of HONORS, SOCIETIES and ORGANIZATIONS: Phi Beta Kappa Alpha Omega Alpha Fellow of the Life Insurance Medical Research Fund Arthur S. Flemming Award Public Health Service/Meritorious Service Medal Public Health Service/Distinguished Service Medal Third Mullin Lectureship/University of Scranton 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 First Annual Institute of International Health & Development Award Gilman Honors Award/New York University Harvey W. Wiley Medal/FDA Commissioner's Special Citation American Society for Clinical Investigation (elected 1980) Association of American Physicians (elected 1989) American Federation for Clinical Research (Eastern Section Councilor) American Society for Clinical Oncology American Association of Immunologists Clinical Immunology Society Editorial Advisory Board for numerous journals Editor, Symposium on HTLV, September 1985, Cancer Research Editor, AIDS: Modern Concepts and Therapeutic Challenges Fellow, American College of Physicians |