Presentation on theme: "Vitamin E and the Risk of Prostate Cancer"— Presentation transcript:
1Vitamin E and the Risk of Prostate Cancer The Selenium and Vitamin E Cancer Prevention Trial (SELECT)Klein, Thompson, Tangen, et al. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14;Zachary LapaquettePharmD CandidateUniversity of Georgia
2Background16% of men will be diagnosed with prostate cancer in their lifetime1Most common type of cancer in U.S. men, other than non-melanoma skin cancer2Second leading cause of cancer-related death in U.S. men
3Background Vitamin E is fat-soluble and has anti-oxidative properties Recommended daily allowance for vitamin E is 22.4IU (15mg) daily3Doses of 50IU/day were shown to decrease prostate cancer incidence in smokers4
4SELECT Trial Randomized, placebo-controlled, multi-center trial Compared selenium 200mcg/day, vitamin E 400IU/day, or both against placeboPlanned follow-up minimum of 7 years and maximum of 12 years
5Inclusion Criteria Healthy Age 50 or older for African Americans, or 55 for all other menNo h/o prostate cancer diagnosisPSA < 4ng/mLNormal DRENo current use of anticoagulantsNo h/o hemorrhagic strokeNormal blood pressureAnticoag, hemorrhagic stroke, blood pressure are due to Vitamin E’s anti-coagulative properties.
6MethodsParticipants without prostate cancer had clinic visits every 6 months; with prostate cancer, annuallyAnnual PSA and DRE were not mandatoryProstate cancer status was determined by self- report at each 6-month visitPathology report, tissue then sent to SELECTNot mandatory, as the benefits of these screens were under debate and were expected to change during the trial.
7MethodsStudy was blinded until 10/23/2008, when participants discontinued use of study agentsNon-blinded follow-up occurred until 07/2011Study facilitators met in 2008 and determined that, according to the data, agents were not effective in reducing prostate cancer, and could not be before the end of the study.Results were published in 2008.
8Statistical AnalysisPrimary end point: Prostate cancer incidence as determined by routine clinical managementOther areas of study: colorectal cancer, lung cancer, all other primary cancers, deaths (all cause), development of diabetes, CVE1- and 2-sided P values given
9Statistical Analysis Proportional hazards model used Unlike linear regression, proportional hazards models do not assume normal distribution and allow for censored dataMen without end-point of interest were censored at last contact dateChi-squared test used to test the difference in the relative risk of diabetes1to compare prostate and other cancer incidence between placebo and each of the 3 study groups with active agents
10ResultsTotal of 35,533 men randomized at 427 centers into placebo (n=7594 had final follow-up data), vitamin E (n=7650), selenium (n=7626), selenium +vitamin E (n=7620)No significant differences in age, race, baseline PSA, or diagnostic testing
11Vitamin E + Selenium (n=8702) ResultsPlacebo (n=8696)Vitamin E (n=8737)Selenium (n=8752)Vitamin E + Selenium (n=8702)No. of prostate cancers529620575555Hazard ratio (99% CI)1.17 ( )1.09 ( )1.05 ( )P value0.0080.180.46AbsoluteRisk9.310.910.19.7Gleason >7, No.133155161164Hazard Ratio(99% CI)1.16 ( )1.21 ( )1.23 ( )0.200.110.08hazard ratio= time factor that study arm will reach outcome measure
12Vitamin E + Selenium (n=8702) ResultsPlacebo (n=8696)Vitamin E (n=8737)Selenium (n=8752)Vitamin E + Selenium (n=8702)All cancers1108119011321149Hazard ratio (99% CI)1.07 ( )1.02 (P value0.130.590.60Diabetes869918913875Relative risk(99% CI)1.05 ( )1.04 ( )0.99 ( )0.290.340.91No secondary endpoint - colorectal cancer, lung cancer, death, CVE, all cancer, or diabetes - had significant results.The 2009 results of the SELECT trial had a diabetes incidence with selenium HR of 1.07
13Authors’ CommentAn explanation for the increased risk of prostate cancer in the vitamin E arm is not apparentThe insignificant increased risk in the vitamin E + selenium arm implies that selenium may have a protective effectThis study is seems to contradict ATBC and PHS II studiesCaution should be used when recommending or studying high doses of micronutrientsHealth effects from these agents may continue even after the intervention is stoppedATBC - smoker one, PHS II - 400IU QOD had no effect on prostate cancer incidencenaturally occurring dietary constituents are part of normal physiology and a U-shaped-dose response curve may exist where deficiency or supraphysiological doses are harmful.
14ConclusionHealthy men with average risk of prostate cancer subjected to contemporary community standards of screening and biopsy who took a common dose of vitamin E have a significantly increased risk of prostate cancer.The increased risk implies that seemingly innocuous yet biologically active substances such as vitamins can cause harmConsumers need be skeptical of health claims for unregulated over-the- counter products in the absence of strong evidence of benefit
15Presenter’s CommentStudy has good reach, but is limited to healthy men 50+ years oldCriticism of study:Did not have best- and worst-case censure analysisData collection dependent on self-report427 research sitesOverall strong studyPlacebo event rate: 529/8696 =
16Presenter’s Comment NNH = 98 Vit E prostate cancer rate: 620/8737 =Placebo prostate cancer rate: 529/8696 =
17Works CitedKlein, Thompson, Tangen, et al. Vitamin E and the Risk of Prostate Cancer: The Selenium and Vitamin E Cancer Prevention Trial. J Amer Med Assoc, Oct 12, 2011; Vol 306, No.14;National Cancer Institute. “A Snapshot of Prostate Cancer.” Sep <http://www.cancer.gov/aboutnci/servingpeople/snapshots/prostate.pdf>National Institutes of Health. “Dietary Supplement Fact Sheet: Vitamin E.” Oct <http://ods.od.nih.gov/factsheets/VITAMINE>Heinonen et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst Mar 18;90(6):440-6.