Initial, independent review of study data from the selenium and vitamin E Cancer Prevention Trial (SELECT), funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health shows that selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer.
The data also showed two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the over 35,000 men age 50 and older in the trial taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium (10 per cent for those taking selenium vs. 9.3 percent taking placebo). Neither of these findings proves an increased risk from the supplements and both may be due to chance.
The Southwest Oncology Group (SWOG), an international network of research institutions, coordinates SELECT at more than 400 clinical sites in the United States, Puerto Rico, and Canada.
Among the specific results highlighted, the five-year rate of prostate cancer diagnosis in the four arms of the study was 4.43 per cent in the placebo arm of the trial, 4.56 per cent in the selenium arm, 4.93 per cent in the vitamin E arm (the highest rate, but one that does not show a statistically significant difference from the placebo arm), and 4.56 per cent in the selenium plus vitamin E arm.
Adherence to the study protocol dropped off from year one to year five (83 per cent adherent vs. 65 per cent at year five), which was expected and did not affect the trial outcome.
SELECT participants received letters in October 2008 explaining the study review and telling them to stop taking their study supplements. Participants will continue to have their health monitored by study staff, which may include regular digital rectal exams and PSA (prostate-specific antigen) tests to detect prostate cancer. Investigators intend to follow the participants for about three years to determine the long-term effects of having taken either supplement or placebo and to complete a biorepository of blood samples that will be used in extensive molecular analyses to give researchers a better understanding of prostate cancer, other cancers, and other diseases of male aging. This additional data collection is a vital part of the study.
Neither the men nor their physicians know which supplements or placebos the men have been taking, a procedure known as blinding or masking. As follow-up of the SELECT participants continues, the participants will continue to be blinded. A blinded follow-up may avoid unintentional bias and potentially false conclusions. However, at the request of a participant, they will be informed which supplement, if any, they received.
"SELECT was always designed as a study that would answer more than a single question about prostate cancer," said Eric Klein, a study co-chair for SELECT, and a physician at the Cleveland Clinic. "As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so."
SELECT was undertaken to substantiate earlier, separate findings from studies in which prostate cancer was not the primary outcome: a 1998 study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer surprisingly showed 32 per cent fewer prostate cancers in men who took the supplement, and a 1996 study of 1,312 men and women with skin cancer who took selenium for prevention of the disease showed that men who took the supplement had 52 per cent fewer prostate cancers than men who did not take the supplement.
Based on these and other earlier findings, in 2001, men were recruited to participate in SELECT. They were randomly assigned to take one of four sets of supplements or placebos, with more than 8,000 men in each group. One group took both selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.
"The SELECT trial owes a tremendous debt to our volunteers, the thousands of men who offered their time and enthusiastic participation, all in the interest of a future when prostate cancer can be prevented," said Laurence H Baker, chairman of the Southwest Oncology Group.