Participants in the largest-ever prostate cancer prevention trial are receiving letters instructing them to stop taking their study pills, the supplements vitamin E and selenium, after an independent review concluded that the trial will not meet its primary endpoint of reducing prostate cancer risk by 25 percent. The 35,000 participants in the NCI-funded Selenium and Vitamin E Cancer Prevention Trial (SELECT) are being asked to continue in the study for approximately 3 more years.

It is important to keep following SELECT participants for a number of reasons, explained Dr. Eric Klein, director of the Center for Urologic Oncology at the Cleveland Clinic and one of the trial's co-chairs. "There is a small chance of a ‘lag effect' of one or both supplements, meaning that their impact on rates of prostate or other cancers may not be apparent for a few more years," he said.

The SELECT executive committee made the decision on the study medications based on the recommendation of the trial's Data Safety Monitoring Committee (DSMC). In its most recent review of the data in mid-September, the DSMC concluded that, with participants having been on their study medications for 5 years on average, there was little chance that one or both supplements would reduce the number of cases of prostate cancer. The review also revealed trends of increased prostate cancer risk with the use of vitamin E and increased adult-onset diabetes risk with the use of selenium, neither of which were statistically significant.

Launched in 2001, SELECT enrolled black men aged 50 or older and white men aged 55 or older - black men have a higher incidence of prostate cancer and are typically diagnosed at an earlier age than white men - to be randomized to one of four arms: two placebo pills, selenium and placebo, vitamin E and placebo, or vitamin E and selenium. Although several earlier laboratory and animal model studies suggested selenium and vitamin E had cancer prevention properties, the primary impetus for launching SELECT was the results from two cancer prevention trials in which each supplement alone seemed to significantly decrease prostate cancer risk. Neither of those trials, however, was focused on prostate cancer prevention, noted Dr. Laurence Baker, professor of medicine and pharmacology at the University of Michigan School of Medicine and chair of the Southwest Oncology Group, which coordinated SELECT.

So SELECT was launched, he continued, to definitively answer whether either supplement alone or in combination could reduce prostate cancer risk. At the more than 400 participating sites, participant enrollment was remarkably swift, with all 35,000 patients enrolled within 3 years.

The slight increase in prostate cancer and diabetes seen thus far could be "due to chance," stressed Dr. Scott Lippman, chair of the Department of Clinical Cancer Prevention at the University of Texas M.D. Anderson Cancer Center, and a co-chair of the SELECT scientific steering committee. This is particularly true for the prostate cancer trend. "There is no biologic rationale to suggest that vitamin E causes prostate cancer," he added.

In addition, noted Dr. Klein, the incidence of prostate cancer in the vitamin E/selenium arm was no different than for men taking placebo. "To explain this, one has to postulate that selenium cancels out any deleterious effect of vitamin E," Dr. Klein said. "This seems unlikely, given that selenium alone had no effect on the incidence of prostate cancer."

Ongoing analyses should help to clarify the findings, they said.

The published evidence for any connection between selenium and diabetes is mixed, so continuing to follow SELECT participants should provide some of the strongest evidence yet on the true effect of selenium on diabetes risk, Dr. Klein continued. 

—Carmen Phillips