Prostate Cancer Prevention Trial (PCPT) Stopped Early by NCI: 25% Reduction in Cancer Risk with Finasteride (PROSCAR)

Washington, D.C., June 23, 2003---The Prostate Cancer Prevention Trial (PCPT) was stopped early ‘in the public interest’, according to trial sponsors at the National Cancer Institute in an early morning press conference. The Merck drug finasteride (PROSCAR) was found to reduce prostate cancer occurrence by 25% compared to placebo in men who participated in the 7-year NCI study. Coincident with the NCI announcement, the New England Journal of Medicine deemed the results of “critical importance” and published findings of the study in an early release on the NEJM website. The article is of keen interest, because with these data, finasteride (PROSCAR) becomes the first thoroughly-tested agent shown to help prevent a disease which is expected to take the lives of nearly 30,000 American men this year.

“Millions of men may benefit from finasteride’s ability to reduce prostate cancer risk,” said Leslie Ford, M.D., who oversaw PCPT for the Institute. The nation’s number one cancer doctor, Andrew C. von Eschenbach, Director of the NCI, called it a “landmark study.” The story appeared on the front page of the New York Times, and it was widely covered by other major news agencies such as CNN and The Wall Street Journal. At the press conference, which will be available online as a webcast for the next year, Dr. Peter Greenwald, Director of Cancer Prevention for the NCI, said, “This trial proves that prostate cancer is at least in part preventable. It is a huge step forward.” On the day of the NCI press conference, USRF Director Leonard S. Marks, M.D., appeared live on CNN television to explain the importance of PCPT.

On a cautionary note, Ian Thompson, M.D., principle investigator of PCPT, said, “Men in the study who developed prostate cancer while taking finasteride were more likely to have high-grade cancers, which, when found in the general population, may spread quickly even if the tumors are small. But, more than 97 percent of men who did develop prostate cancer during this study had early-stage cancers, which are most often curable.” The significance of this cautionary note cannot be known until information about the biological behavior of these high-grade cancers becomes available. The Gleason Grading System for prostate cancer is explained here.

The reason men on finasteride had more high-grade tumors is currently unknown, but the researchers are studying several possibilities. The drug affects the appearance of prostate cancer cells, and this may lead to a false estimate of tumor grade, which is determined visually by a pathologist. Another possible explanation being examined is whether finasteride truly causes more aggressive tumors to develop—either by preventing only low-grade tumors, or by making the prostate gland more favorable to aggressive tumors. A USRF study examining the long-term effects of finasteride on prostate tissue, determined by serial biopsy, was published in 1999.

PCPT, which was a $73 million project, is the most important prostate cancer chemoprevention trial ever completed. The trial was coordinated for the NCI by the Southwest Oncology Group, which is one of the world’s largest clinical trials organization. The first man was enrolled in October of 1993, and the trial was stopped on March 3, 2003. At 221 study sites across the nation, approximately 25,000 men were enrolled and 18,900 completed randomized treatment until the study was stopped 15 months early. By the close of the study, prostate cancer had been found in about 18 percent of the men who took finasteride, or 803 men out of 4,368. About 24 percent of men who took placebo, or 1,147 men out of 4,692, also had been diagnosed with prostate cancer. Many of the men with cancer had normal prostate exams and PSA levels, and the disease was found only because the trial required an end-of-study biopsy. Details of the study are available in the NEJM publication and also on this NIH website. The key figure of PCPT is shown here.

Three other large, long-term prostate cancer prevention trials are currently in the enrollment phase:
(1) a study undertaken by GlaxoSmithKline involving the drug dutasteride (AVODART).

(2) a study undertaken by Merck involving the drug rofecoxib (VIOXX).

(3) the SELECT trial undertaken by the NCI, involving selenium and vitamin E.