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Addressing Validity

Dr. Peter Nowell

tal, Boston, who cochaired the IOM report committee with Rowley. "If they can improve their diagnoses, if they can improve their therapies... they should be made use of." Sklar expressed concern about clinicians adhering so strongly to the adage "do no harm" that they fail to take advantage of genetic markers. The use of genetic markers essentially causes no harm to patients, Sklar said. "There are no side effects from diagnostic tests." Rather, questions that have arisen have been concerned with interpreting the data generated.

Fear and Resist The use of genetic markers will not "penetrate" beyond major medical centers until clinicians become convinced of their value, said Peter Nowell, M.D., of the University of Pennsylvania and codiscoverer of the Philadelphia chromosome. He notes a schism between advocates who oversell genetic markers and clinicians who resist or even fear them. Nowell recommends a course in between: Clinicians should use genetic markers where they have proven value, such as in the diagnosis of chronic

NCI will address questions about the validity of techniques used to assay genetic markers. In March it requested applications from centers to evaluate the usefulness of various prognostic techniques. Although declining to say which techniques will be evaluated, Taube said the first studies will look at early stage breast cancer and B2 and C stages of colon cancer. Much of the research to date has involved diagnosis, prognosis, and monitoring, but genetic markers also hold promise for other areas of cancer management. Vogelstein, for instance, considers the most important recent advance to be the discovery of genes which, when inherited in mutant form, predispose persons to colorectal cancer. Virji pointed out the possibility of developing screens that can detect gene products sloughed off by dead tumor cells in serum or elsewhere. The next big step, according to Nowell, may be toward therapies directed at genetic markers. Although the experts reached no consensus about where the next advances in the clinical use of genetic markers will be, most were optimistic. "Fishing in these waters is going to yield some real opportunities," Slamon said. But, he cautioned, "everything needs to be proven, and it needs to be proven in large clinical trials that are appropriately conducted. The results will speak for themselves." —By Hugh Mclntosh

NCI Strengthens Commitment to Prostate Cancer The National Cancer Institute increased funding for prostate cancer research after realizing that, although incidence and mortality figures for prostate and breast cancers were roughly comparable, prostate cancer was receiving a fraction of the funding. "NCI has made prostate cancer a high priority," said Samuel Broder, M.D., director of the institute, in addressing the National Cancer Advisory Board in January. "For certain cancers like prostate, we believe a targeted, stimulated approach is needed." NCI funding for prostate cancer research in 1992 is expected to reach $28 million - double what it was a year ago. Prostate cancer is the most commonly diagnosed cancer in American men, and accounts for 25% of all cancer diagnoses in black men. Prostate cancer risk increases faster with age than risk for any other form of cancer.

Genetic Changes The steps that lead prostate cells to become cancerous have not been defined. On the genetic front, changes on chromosomes 10,16, and 17 have been associated with prostate cancer. W. Marston Linehan, M.D., head of NCI's Urologic Oncology Section, and colleagues are examining the p53 and RB genes. "In in vitro prostate cancer cell lines, we've seen abnormalities at p53 and RB genes, and have shown that genetic transfer of these genes back into the cell lines in vitro alters their tumorigenicity," Linehan said. He and other NCI researchser are planning studies to pinoint the disease genes. Research planned in other Journal of the National Cancer Institute

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myelogenous leukemia. And clinicians in research settings should also use promising markers in validation studies. "We should be using selectively some of these to gather the information, so that 5 yearsfromnow we'll be able to look back and say whether, in fact, this information has been of value to us," Nowell said.

News News divisions of NCI will also try to discover the steps prostate cells take towards becoming cancerous, and how this progression might be halted.

Prostate cancer also appears in many men in an innocuous form. Linehan and other researchers are hoping to find genetic differences between the indolent form, which is not threatening to the life of the patient, and more aggressive prostate cancer. Autopsy studies have shown that more than 30% of men over age 50 have evidence of prostate cancer, yet the vast majority of these cancers will never become a threat. "We need to know in which [cases] it is appropriate to recommend surgery or radiation, and we need more powerful tools to perform early detection and to understand in which individuals intervention is appropriate," said Linehan. The Prostate, Lung, Colorectal, and Ovarian screening trial (PLCO) will screen 37,000 men and 37,000 women aged 60 to 74 (balanced with 74,000 unscreened controls). For prostate screening, PLCO will use digital rectal exams

Dr. W. Marston Lineitai _

Vol. 84, No. 7, April 1, 1992

Prevention Trial According to NCI's Otis Brawley, M.D., a prostate cancer prevention trial will evaluate the drug Proscar, enrolling 12,000 to 18,000 men at high risk for prostate cancer. Proscar decreases the synthesis of dihydrotestosterone, which has been implicated in tumor promotion. NCI hopes to enroll patients this fall for the 10-year study. NCI also is encouraging research in prostate cancer by establishing Specialized Programs of Research Excellence (SPORE) grants. The grants will be funded at $2.5 million over 3 years to institutions willing to make a strong commitment to concentrated research on all aspects of a particular cancer. At least two of the seven or more SPOREs, which will be awarded in end of FY 1992, are expected to be earmarked for prostate cancer. —By Nancy Volkers

Nation Calls for Increased Yew Tree Collection Even though cooperation between federal and private agencies has resulted in a significant increase in yew bark collection, Congress and environmentalists are calling for expanded efforts to reduce waste and increase retrieval, thereby expanding availability of taxol. Because of the shortage of taxol, only 500 patients per year were receiving taxol in clinical trials before collaboration began between the Bureau of Land Management, U.S. Forest Service, National Cancer Institute, and Bristol-Myers Squibb, the company that develops taxol, testified Bruce Chabner, M.D., director of NCI's Division of Cancer Treatment, at a recent congressional hearing. This year, 8,000 to 10,000 patients will be able to receive taxol with the 1991 supply harvested through the cooperative effort, he said. "The combined potential population of patients

Dr. Bruce Chabner

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and prostate specific antigen measurements, with positive results in either case leading to the use of further diagnostic methods. The 16-year, $87-million study, set to begin in 1993, will provide valuable information on the early detection of prostate cancer as well as a base for further studies involving the screened population. Current clinical trials in prostate cancer include evaluating radical prostatectomy versus radiotherapy, chemotherapy versus observation after radiotherapy, and hormone manipulation versus observation after radical prostatectomy. Current phase n trials include work with strontium, piroxantrone, taxol, didemnin B, 5-FU plus interferon, and iproplatin. Phase II trials being planned include 5-FU plus leucovorin, 4-hydroxyphenylretinamide and all-trans-retinoic acid. A future study will compare suramin to a series of new agents. Trials are also being planned for men with elevated PSA levels.

NCI strengthens commitment to prostate cancer.

News News Addressing Validity Dr. Peter Nowell tal, Boston, who cochaired the IOM report committee with Rowley. "If they can improve their diagnose...
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