In perhaps the largest cancer chemoprevention trial ever conducted, researchers have found that supplementation with vitamin E or selenium, alone or in combination, was not associated with a lower risk of prostate cancer or other cancers.
This study, along with another cancer prevention study, will be published in the January 7 issue of JAMA, the Journal of the American Medical Association, and both reports are being released early online because of public health implications.
The number of prostate cancer deaths in the United States has declined in recent years, but this cancer remains one of the most common malignancies in U.S. men, with approximately 186,000 new cases and 29,000 deaths (the second leading cause of cancer death) estimated for 2008. An effective prevention strategy for prostate cancer would have substantial public health benefits, according to background information. Previous studies have indicated the potential of selenium and vitamin E for preventing prostate cancer.
Scott M. Lippman, M.D., of the University of Texas M. D. Anderson Cancer Center, Houston, and Eric A. Klein, M.D., of the Cleveland Clinic Lerner College of Medicine, Cleveland, and colleagues conducted the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to examine the effects of selenium and vitamin E, alone or in combination, on the risk of prostate cancer and other health outcomes in relatively healthy men. The trial included 35,533 men, age 50 years or older for African-American men and age 55 years or older for other men at the start of the study, from the U.S., Canada, and Puerto Rico. The participants were randomly assigned to receive one of four interventions between August 2001 and June 2004 for a planned minimum follow-up of 7 years: selenium (200 ìg/day); vitamin E (400 IU/day), selenium + vitamin E, or placebo.
On September 15, 2008, the independent data and safety monitoring committee recommended the discontinuation of study supplements because the alternative hypothesis of no evidence of benefit from either study agent was convincingly demonstrated and there was no possibility of a benefit to the planned degree with additional follow-up. The notice to discontinue study supplements went out to all active study sites on October 23, 2008, when median (midpoint) overall follow-up was 5.46 years.
The researchers found that there were no statistically significant differences in the absolute numbers (or 5-year incidence rates) of prostate cancer diagnoses between the four groups: placebo, 416 cases (5-year rate of 4.43 percent); selenium, 432 cases (4.56 percent); vitamin E, 473 cases (4.93 percent); selenium + vitamin E, 437 cases (4.56 percent). There were nonsignificant increased risks of prostate cancer in the vitamin E group and type 2 diabetes mellitus in the selenium group, but not in the selenium + vitamin E group.
"In conclusion, SELECT has definitively demonstrated that selenium, vitamin E, or selenium + vitamin E (at the tested doses and formulations) did not prevent prostate cancer in the generally healthy, heterogeneous population of men in SELECT. These data underscore the prudence that is needed in considering recommendations to use agents for the prevention or control of disease in the absence of convincing clinical trial results. These findings also compel the medical research community to continue the search for new, effective agents for prostate cancer prevention," the authors write.
Editorial: Randomized Trials of Antioxidant Supplementation for Cancer Prevention-First Bias, Now Chance-Next, Cause
In a JAMA editorial, Peter H. Gann, M.D., Sc.D., of the University of Illinois at Chicago, comments on the "disappointing news" that two major trials (SELECT and Physicians' Health Study II, which were "conceived during the wave of hope" of earlier studies suggesting that cancer might be prevented by selenium or vitamin E) showed that neither selenium nor vitamin E produced any reduction in prostate cancer or other cancers.
"… single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations. It may be time to give up the idea that the protective influence of diet on prostate cancer risk … can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men. … On the other hand, nonpharmacological dietary prevention of prostate cancer is probably more complex and may involve certain inconvenient truths. Fortunately, no dietary change this profound is likely to be beneficial for prostate cancer alone. If it requires whole foods, extracts, or dietary patterns, it may be necessary to give up the reductionist need to know which molecule is most responsible and perhaps give up the notion of placebo controls as well."
"Epidemiology teaches that every statistical association has only 3 possible explanations: bias, chance, and cause. Regarding nutritional prevention of prostate cancer, first-generation phase 3 trials were too reliant on biased interpretation of prior research, second-generation trials may have been too reliant on chance, yet there is every reason to believe that the next generation will have a firmer basis for causal hypotheses. Until then, physicians should not recommend selenium or vitamin E-or any other antioxidant supplements-to their patients for preventing prostate cancer."