The prostate cancer trials: SELECT, PHSII
No effects of selenium and vitamins in prostate cancer clinical trials
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomly assigned over 35,000 men to receive daily selenium, vitamin E, both, or placebo. After almost five and a half years, no significant differences were observed between any of the groups in relation to prostate cancer risk.
In the second study – the Physicians' Health Study II – about 15,000 men were randomly assigned to vitamin E supplements every other day and daily vitamin C supplements. Over the eight tears of follow-up no effects on either prostate cancer or overall cancer.
The results, to be published in the 7th January 2009 issue of the Journal of the American Medical Association (JAMA), are yet more “disappointing” news for the supplements and nutrition industry. Major consumer media outlets are already running headlines like: “Vitamins 'do not cut cancer risk'” (BBC).
JAMA released the studies early online “because of public health implications”.
The dietary supplements industry has already responded to the findings. Andrew Shao, Ph.D., vice president, scientific and regulatory affairs, for the trade association the Council for Responsible Nutrition (CRN) said: “Despite the results from recent studies, there is additional research that suggests antioxidant vitamins may play a role in helping to lower the risk of chronic diseases.
“However, vitamin supplements are just one piece of the puzzle, which may be why we didn’t see the results we anticipated from the recent clinical trials.”
Dr Pamela Mason, scientific advisor to the Health Supplements Information Service (HSIS) went further, and said: “Looking at the trials in brief, both represent the latest in a long line of studies that have attempted to use vitamins and trace elements like pharmacological agents. Vitamins and trace elements are not intended to be used like drugs.”
To read further comment from various sources, please click here.
History had provided hope
The results are published 12 years after those of the Nutritional Prevention of Cancer trial found that selenium supplementation may reduce the incidence of prostate cancer in men by a whopping 65 per cent.
Moreover, in 1994, the alpha-tocopherol, beta-carotene (ATBC) Cancer Prevention Trial found that vitamin E supplements may reduce the occurrence of the cancer by 35 per cent.
SELECT details
Building on the results of these previous studies, SELECT included 35,533 men, age 50 years or older for African-American men and age 55 years or older for other men from the U.S., Canada, and Puerto Rico.
Participants were randomly assigned to receive selenium (200 micrograms per day), vitamin E (400 IU per day), selenium plus vitamin E, or placebo for seven years.
The researchers, led by Scott Lippman, MD, from the University of Texas M. D. Anderson Cancer Center, Houston, discontinued the study after 5.46 years after finding no convincingly evidence of benefit was demonstrated and the researchers deemed no benefit with additional follow-up.
Overall, there were no statistically significant differences in the absolute numbers (or five-year incidence rates) of prostate cancer between the four groups. Indeed, all groups had between 416 and 473 cases, and a five-year incidence rate of between 4.43 and 4.93 per cent.
Worryingly, a small nonsignificant increase in the risk of prostate cancer was observed in men in the vitamin E only group, and a small nonsignificant increase in type-2 diabetes in the selenium group.
"SELECT has definitively demonstrated that selenium, vitamin E, or selenium plus vitamin E (at the tested doses and formulations) did not prevent prostate cancer in the generally healthy, heterogeneous population of men in SELECT,” wrote the researchers.
“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,” they concluded.
PHSII details
Researchers led by J. Michael Gaziano, MD, from Brigham and Women's Hospital recruited 14,641 male physicians in the US, and randomly assigned them to receive supplements of 400 IU of vitamin E every other day, or 500 mg of vitamin C daily, or placebo for about eight years .
Results of the randomised, placebo-controlled trial found 1,008cases of prostate cancer and 1,943 cases of any cancer. Compared with placebo, neither vitamin had any effect on the incidence of prostate cancer or total cancer.
In a challenge to the results of SELECT, Gaziano and his co-workers said: “It is reassuring that there was not a clear signal of harm for either agent.”
Commenting on the limitations, the researchers said: “The study was conducted in a well-nourished population, and thus, these results may not preclude potential benefits in less well-nourished populations.
“One concern is the choice of dose used. It is not feasible to test multiple doses in these large-scale trials. The doses of vitamin E and C in the PHS were chosen because they were in the range of those commonly in use, because they did not have known major adverse effects that would impact adherence, and because their safety data were sound - a critical issue when conducting a trial by mail.
“The form of vitamin E chosen for our study was synthetic alpha-tocopherol, the most abundant component of natural vitamin E. However, in nature, vitamin E is composed of both alpha- and gamma-tocopherol. Gamma-Tocopherol has been postulated to possibly play a more important role in prostate cancer protection,” they added.
To read reaction to these studies, please click here.
Sources: Journal of the American Medical Association2009, Volume 301, Number 1, doi:10.1001/jama.2008.864“Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other CancersThe Selenium and Vitamin E Cancer Prevention Trial (SELECT)”Authors: S.M. Lippman, E.A. Klein, P.J. Goodman, M.S. Lucia, et al.
Journal of the American Medical Association2009, Volume 301, Number 1, doi:10.1001/jama.2008.862“Vitamins E and C in the Prevention of Prostate and Total Cancer in Men - The Physicians' Health Study II Randomized Controlled Trial”Authors: J.M. Gaziano, R.J. Glynn, W.G. Christen, T. Kurth, et al.
