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embalmers and funeral directors who had routine exposure to formaldehyde and other chemicals. A case-control study of these cancers, which includes a detailed industrial hygiene assessment of exposures occurring during embalming, has been initiated to clarify these associations.
Organic solvents are widely used in industry, and several have been shown to cause cancer in laboratory animals. Investigations have recently been completed to evaluate cancer risks associated with exposures to certain solvents. A study of U.S. Coast Guard marine inspectors uncovered excess mortality from cancer and cirrhosis of the liver, leukemia, and motor vehicle accidents. Risk from these causes of death rose with cumulative level of exposure to chemicals. During Inspection of vessels, marine inspectors may come into contact with various chemicals, but particularly organic solvents that are often transported by ship. In another study, an excess of lymphatic and hematopoietic cancer was noted among dry cleaners. Although several solvents have been used in dry cleaning over the years, carbon tetrachloride, petroleum solvents, and perchloroethylene have been preferred. Organic solvents are also widely used in the repair and maintenance of aircraft. The NCI recently completed an evaluation of civilian workers at an Air Force base engaged in these activities. No convincing association was noted between any cancer and exposure to trichloroethylene, a widely used degreaser.. Mortality from multiple myeloma and NHL, however, was elevated among workers exposed to a variety of other solvents. This investigation is being extended to further evaluate these associations.
Several investigations have evaluated the risk of lung cancer from occupational exposures. Lung cancer was excessive among workers in a chromium pigment factory, where zinc and lead chromates exposures occur, rising to over three-fold among those exposed for 10 or more years. A nearly four-fold excess of lung cancer was observed among underground hematite miners in China with exposure to radon and silica. In a study from Missouri, the risk of adenocarcinoma of the lung was elevated among carpenters, cabinet and furniture makers, plumbers, and printers. The association between this histologic type of lung cancer and potential exposure to wood dusts is intriguing, since adenocarcinoma is also the type of nasal and sinus cancer most strongly associated with exposure to wood dust. In another case-control study, lung cancer was associated with employment in several motor exhaust-related occupations, including truck drivers, heavy equipment operators, taxi drivers, and mechanics.
High-priority ongoing investigations include cancer risks among lawn care workers and county noxious weed applicators from occupational exposures to herbicides, among chemical workers exposed to acrylonitrile, among workers in dusty trades exposed to silica, among workers in China exposed to benzene, and mesothelioma risk among workers in a variety of occupations where asbestos is used.
Question. Please provide a line item budget with full abstracts for current and proposed NCI funding in the following
B. Innovative Therapies
1. Best case studies
Answer. Demonstration of the effectiveness of new anticancer treatments requires their systematic testing in clinical trials. Major NCI - sponsored clinical trials are conducted through the clinical Cooperative Groups, a nation-wide consortium of medical centers whose physicians are dedicated to identifying the benefits as well as the toxicities associated with new cancer therapies. Support for NCI clinical trials is as follows:
As I mentioned earlier, the Investigational Drug Branch of NCI's Cancer Therapy Evaluation Program (CTEP) is responsible for the coordination and evaluation of NCI-sponsored extramural trials of new cancer therapies as well as for evaluation of unconventional cancer treatments. In studies where there are unusual or unexpected results, CTEP is also available, at the investigator's request, to audit the results of a cancer clinical trial. Such reviews are performed by program personnel from CTEP's Clinical Investigations and Investigational Drug Branches. The budget for these two Branches in FY 1991 is estimated to be $2.7 million,
In the evaluation of investigational therapies, CTEP will also be asked from time to time to evaluate unconventional therapies as well. In an effort to provide a "level playing field," CTEP has undertaken special efforts to provide guidance to proponents of unconventional therapies regarding the conduct and analysis of clinical trials.
CTEP is in the process of developing a short document on cancer clinical trials methodology that can be understood by those not engaged in formal clinical trials. This document will provide procedures for the development of a "best case series" and small pilot studies that might provide information about those patients who are likely to have experienced antitumor benefit from unconventional treatment.
Question. Dr. Broder, over the past several months, I have read many recent accounts of tremendous progress which has been made in cancer research--gene therapy, how cancer spreads and many other examples. Could you highlight for me and the Committee, in laymen's terms, 5 of the most crucial advances over the year or
two, and what difference those advances have or will make in people's lives.
Answer. In addition to the advances described in the field of gene therapy which opens up the possibility direct alterations in the body to replace defective or missing genes and which allow for specific, highly targeted use of natural disease fighting entities to attack tumors, there are many other areas of progress which are directly relevant to patients. Once cancer patients were treated primarily with surgery and/or radiation. Then chemotherapy was gradually added and followed by combinations of drugs. Now drugs are being used at different points in the therapy adjuvant to surgery or radiation. NCI -supported research has developed a number of adjuvant treatments for some common tumors. Some therapies are specific to a certain stage of a cancer, but directly or indirectly they affect the outlook for patients. These recent therapeutic improvements offer new hope for the 150,000 patients with breast cancer, particularly the 60,000 who have node negative disease, and the 157,000 with colon and rectum cancer. The latest research advance improves survival and reduces relapse for patients with rectal cancer and promises to save an additional 3,000 lives a year.
A new neoadjuvant treatment involving chemotherapy and radiation before surgery, suggests that patients with advanced esophageal cancer, some 11,000 new cases annually, substantially increase their disease-free survival under this treatment regimen compared to standard treatments.
Another achievement is the accelerated development of a promising new drug which has shown promising results in ovarian, breast, and other cancers. This drug, taxol, is isolated from the bark of the western yew. Major efforts are being made to solve the problems of supply. Since this drug operates at the level of the cell cycle, it provides a new approach for patients whose disease has proven resistent to other forms of treatment.
A potentially important breakthrough has occurred due to basic cancer research. Various studies supported by NCI have shown the importance of a suppressor gene, p53, in a number of types of cancer. An NCI-supported researcher at Johns Hopkin's University has recently replaced a missing gene in the laboratory and reversed colon cancer in the test tube. This gene appears to be important in lung cancer as well. Recently, NCI -scientists found that it was instrumental in the inherited Li-Fraumeni syndrome which is characterized by numerous kinds of tumors. Finding a critical gene like this and beginning to learn how to replace or repair holds the possibility that rather than relying on treatment as we know it now, we will be able to replace suppressor genes to allow the body's own mechanisms to stop the cancer in its tracks.
NCI has recently reported on important studies further supporting the link between diet and health. For instance, the Nurses Health Study followed 90,000 women for six years and showed that a low fiber and high fat diet increases risk of colon cancer. A number of studies support the hypothesis that high fat diets play a role in breast cancer. NCI is beginning a feasibility study in minority groups which will eventually help to establish
solid data on this important subject. All of this information on the role of diet and that of specific dietary components, such as fat, will help provide the public with choices to improve health.
On January 23, 1991, NCI and the Susan G. Komen Foundation, with considerable support from the Congress, sponsored a second Women's Leadership Summit entitled "Women in the Workplace: The Challenge of Breast Cancer." Marilyn Quayle gave the keynote address and Barbara Bush held a reception at the White House for those who attended the Summit which, like last year's Summit, took place on Capitol Hill. Over 200 corporate leaders attended to hear scientists talk about breast cancer research. Presentations on worksite programs were also made. This Summit helped to focus attention on the subject of breast cancer and to help carry the message and stimulate programs in order to reach many more women.
IMPACT OF BUDGET LEVELS
Question. Dr. Broder, you are aware of this Committee's commitment to the medical research programs at the NIH, particularly those at the NCI. I have recently been told that the NCI budget has actually decreased by 6 percent when corrected for inflation while the other programs have increased by 27 percent. Can you describe for me how that has translated to many of the programs which are unique to your Institute--such as the Community Clinical Oncology Program, Cancer Prevention and Control Program and Cancer Centers?
Answer. The NCI budget has decreased in constant dollars since 1980. The NCI budget has decreased approximately six percent in 1980 dollars, while the overall NIH budget has increased by about 27 percent. These percentage figures were obtained using the 1980 deflator for 1991 (1.9088) from the Biomedical Research and Development Price Index (BRDPI). Overall, in current dollars the NCI budget has increased by $852 million or 89 percent between FY 1980 and the request for FY 1992 and the NIH budget has increased by 156 percent. of the major mechanisms used by NCI, wo have kept pace with the growth of NIH in 1980 constant dollars. Research Project Grants have grown by about 29 percent, which is quite similar to the growth for this mechanism across the NIH. This is a result of the stabilization objectives set by NIH in recent years. Efforts funded through the Intramural Research mechanism have also grown in 1980 constant dollars, by approximately 22 percent. Although the addition of monies for AIDS - specific new initiatives is not factored out for this figure, for cancer-specific activities, the intramural program has fallen by about five percent in 1980 constant dollars.
Other NCI mechanisms have experienced a decline in constant dollars, although they have continued to produce significant. results. These mechanisms are either unique to NCI or are used predominantly by NCI. One major example is the NCI Cancer Prevention and Control Program. A vital component of the Institute's research effort against cancer, the Cancer Prevention and Control Program has experienced a 33 percent decline in 1980 constant dollars. The Community Clinical Oncology Programs (CCOPs), which are a part of the Cancer Prevention and Control Program, have in turn lost about 8 percent.
Other NCI mechanisms have also experienced a loss in purchasing power.
The clinical Cooperative Groups program has declined by about 32 percent in 1980 constant dollars. This is the mechanism that NCI uses for major clinical trials. The budget for NCI research and development contracts has declined by nearly one half during the same period. These contracts are the most effective means for accomplishing certain very important NCI operations, including the Surveillance Epidemiology End Result (SEER) program, the Cancer Information System (CIS) and the development of monoclonal antibodies for use in cancer treatment (under the Biological Response Modifier Program). Cancer Centers have fared somewhat better, losing about 14 percent of their purchasing power since 1980. This loss in purchasing power has slowed our capability to expand the Institute's nationwide cancer information dissemination and community outreach network as well as the geographic dispersion of basic and clinical cancer research.
NCI PROFESSIONAL JUDGMENT
Question. In your professional judgment, how much money above the President's Budget does the NCI need to continue to stabilize its grants and begin to address these program cuts which have occurred over the past decade?
Answer. In my professional judgment, the primary consideration for funding within the Cancer Program is a requirement to develop a balanced program, one that will take full advantage of all research findings with the goal of a rapid translation of basic research successes into clinical applications. Our highest priority has always been the support of basic research and it will always remain an extremely high priority for NCI. Given today's biotechnology revolution, we need to adapt findings to the immediate benefit of the cancer patient as well as to develop interventions that are effective in the prevention of cancer. One measure to initiate such a capability would be stable support for the entire Program, especially research grants, cancer centers, clinical trials, intramural research, and prevention and control. To support approximately 35 percent of competing grants, the same percentage as was funded in 1980, as well as to restore those mechanisms that have not kept pace with inflationary requirements during the past decade, would require approximately $320 million over the 1992 President's Budget.
1980 SPENDING LEVEL
Question. Dr. Broder, how much would it take to get the NCI back to its 1980 spending level?
Answer. For the National Cancer Institute to reach its 1980 real spending level, those NCI mechanisms that have experienced a loss in purchasing power since 1980 would require an increase of close to 20 percent over current budget for Cancer Centers, approximately 50 percent for both Clinical Cooperative Groups and Cancer Prevention and Control, and approximately 90 percent for Research and Development Contracts. This would result in a request of approximately $320 million beyond the 1992 President's Budget.