TY - JOUR
T1 - SELECT
T2 - The selenium and Vitamin E Cancer Prevention Trial: Rationale and design
AU - Klein, E. A.
AU - Thompson, Ian M
AU - Lippman, S. M.
AU - Goodman, P. J.
AU - Albanes, D.
AU - Taylor, P. R.
AU - Coltman, C.
N1 - Funding Information:
Recent research suggests that selenium and vitamin E are promising candidates for prostate cancer prevention.8 Compelling data supporting the use of both agents in this setting come from secondary analyses of large-scale chemoprevention trials for other cancers.9,10 These analyses have suggested that selenium and vitamin E may prevent the development or progression of prostate cancer. SELECT, a Phase III randomized, double-blind, placebo-controlled, population-based clinical trial has been designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer. SELECT is funded by the National Cancer Institute and will be coordinated by the Southwest Oncology Group, with participation form major cooperative groups in North America, including ECOG, CALGB, NCCTG, RTOG, the Veterans Administration, and the Canadian Urologic Oncology Group. The trial is anticipated to open in the fourth quarter of 2000.
PY - 2000
Y1 - 2000
N2 - Prostate cancer is the commonest non-skin malignancy in the United States and has a substantial mortality rate despite the use of PSA-based screening. Furthermore, therapy for prostate cancer by surgery, radiotherapy or hormonal manipulation carries a significant risk of treatment-related morbidity. Recent analysis of secondary endpoints of several large-scale randomized prospective clinical trials for other malignancies has suggested that selenium or vitamin E may result in a decreased incidence and mortality from prostate cancer. In vitro and preclinical studies of these antioxidants support this hypothesis. This review outlines the rationale and design of SELECT, the Selenium and Vitamin E Cancer Prevention Trial, designed to test the hypothesis that selenium or vitamin E alone or in combination can reduce the clinical incidence of prostate cancer in a population-based cohort of men at risk. SELECT is a phase III, randomized, double-blinded, prospective, 2 x 2 factorial clinical trial which will randomize 32,400 healthy men with normal DRE and serum PSA to one of four study arms: selenium alone, vitamin E alone, selenium + vitamin E, or placebo. Study agents will be taken orally for a minimum of 7 and maximum of 12 y with assessments of general health, incident prostate cancer and toxicity performed at 12 month intervals. Under the assumptions described, the detectable risk reduction is 25% for an effective single agent relative to placebo, with an additional 25% reduction for the combination relative to an effective single agent. The estimated power for the comparison of a single agent vs placebo is 96% and the power for the comparison of an effective single agent vs combination is 89%. Secondary endpoints will include prostate cancer-free survival, all-cause mortality, and the incidence and mortality of other cancers and diseases potentially impacted by the chronic use of selenium and vitamin E. Other trial objectives will include periodic quality of life assessments, assessment of serum micronutrient levels and prostate cancer risk, and studies of the evaluation of biological and genetic markers with the risk of prostate cancer.
AB - Prostate cancer is the commonest non-skin malignancy in the United States and has a substantial mortality rate despite the use of PSA-based screening. Furthermore, therapy for prostate cancer by surgery, radiotherapy or hormonal manipulation carries a significant risk of treatment-related morbidity. Recent analysis of secondary endpoints of several large-scale randomized prospective clinical trials for other malignancies has suggested that selenium or vitamin E may result in a decreased incidence and mortality from prostate cancer. In vitro and preclinical studies of these antioxidants support this hypothesis. This review outlines the rationale and design of SELECT, the Selenium and Vitamin E Cancer Prevention Trial, designed to test the hypothesis that selenium or vitamin E alone or in combination can reduce the clinical incidence of prostate cancer in a population-based cohort of men at risk. SELECT is a phase III, randomized, double-blinded, prospective, 2 x 2 factorial clinical trial which will randomize 32,400 healthy men with normal DRE and serum PSA to one of four study arms: selenium alone, vitamin E alone, selenium + vitamin E, or placebo. Study agents will be taken orally for a minimum of 7 and maximum of 12 y with assessments of general health, incident prostate cancer and toxicity performed at 12 month intervals. Under the assumptions described, the detectable risk reduction is 25% for an effective single agent relative to placebo, with an additional 25% reduction for the combination relative to an effective single agent. The estimated power for the comparison of a single agent vs placebo is 96% and the power for the comparison of an effective single agent vs combination is 89%. Secondary endpoints will include prostate cancer-free survival, all-cause mortality, and the incidence and mortality of other cancers and diseases potentially impacted by the chronic use of selenium and vitamin E. Other trial objectives will include periodic quality of life assessments, assessment of serum micronutrient levels and prostate cancer risk, and studies of the evaluation of biological and genetic markers with the risk of prostate cancer.
KW - Chemoprevention
KW - Prostate cancer
KW - Selenium
KW - Vitamin E
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U2 - 10.1038/sj.pcan.4500412
DO - 10.1038/sj.pcan.4500412
M3 - Review article
AN - SCOPUS:0033638653
SN - 1365-7852
VL - 3
SP - 145
EP - 151
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 3
ER -