• Effect on the clinical incidence of cancer [ Designated as safety issue: No ]
• Effect on cancer-free survival, overall survival and serious cardiovascular events [ Designated as safety issue: No ]
• Quality of life [ Designated as safety issue: No ]
• Association of biological molecular markers with cancer risk [ Designated as safety issue: No ]
• Relationship between effects on cancer risk and genetic factors [ Designated as safety issue: No ]
• Effects in terms of intake of other nutrients, foods, and dietary supplements [ Designated as safety issue: No ]
• Effect of other dietary nutrients and dietary patterns on cancer risk [ Designated as safety issue: No ]
• Effects on the reduction of Alzheimer's disease incidence [ Designated as safety issue: No ]
• Reduction in the risk of age-related macular degeneration or cataract [ Designated as safety issue: No ]

• Effect on the clinical incidence of cancer
• Effect on cancer-free survival, overall survival and serious cardiovascular events
• Quality of life
• Association of biological molecular markers with cancer risk
• Relationship between effects on cancer risk and genetic factors
• Effects in terms of intake of other nutrients, foods, and dietary supplements
• Effect of other dietary nutrients and dietary patterns on cancer risk
• Effects on the reduction of Alzheimer's disease incidence
• Reduction in the risk of age-related macular degeneration or cataract

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known which regimen of selenium and/or vitamin E may be more effective in preventing prostate cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of selenium and vitamin E, either alone or together, in preventing prostate cancer.

OBJECTIVES:

• Compare the effect of selenium and vitamin E administered alone vs in combination on the clinical incidence of prostate cancer.
• Compare the effect of these prevention regimens on the incidence of lung cancer, colorectal cancer, and all cancers combined in participants on this study.
• Compare the effect of these prevention regimens on prostate cancer-free survival, lung cancer-free survival, colorectal cancer-free survival, cancer-free survival, overall survival, and serious cardiovascular events in these participants.
• Compare the quality of life of participants treated with these regimens.
• Determine the association of biological molecular markers with the risk of prostate cancer, lung cancer, and colon cancer in these participants.
• Determine the relationship between the effects of these regimens on prostate cancer risk and genetic factors in these participants.
• Determine whether the effects of these regimens on prostate cancer risk are conditional upon pre-study use of these supplements by these participants.
• Determine whether the effects of these regimens are conditional upon intake of other nutrients, foods, and dietary supplements by these participants.
• Determine the effect of other dietary nutrients and dietary patterns on prostate cancer risk in these participants.
• Determine the effects of these regimens on the reduction of Alzheimer's disease incidence in these participants.
• Determine whether these regimens reduce the risk of age-related macular degeneration or cataract in these participants.

OUTLINE: This is a randomized, double-blind, multicenter study. Participants are randomized to one of four prevention arms.

• Arm I: Participants receive 2 different oral placebos once daily.
• Arm II: Participants receive oral selenium and oral placebo once daily.
• Arm III: Participants receive oral vitamin E and oral placebo once daily.
• Arm IV: Participants receive oral selenium and oral vitamin E once daily. Treatment continues for 7-12 years in the absence of unacceptable toxicity or diagnosis of prostate cancer.

Quality of life is assessed at baseline and then at 1, 3, 5, and 7 years.

Participants are followed annually.

PROJECTED ACCRUAL: A total of 32,400 participants (8,100 per prevention arm) will be accrued for this study within 5 years.

• Dietary Supplement: selenium
• Dietary Supplement: vitamin E

• Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD 3rd, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH, Coltman CA Jr. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 7;301(1):39-51. Epub 2008 Dec 9.
• Hoque A, Albanes D, Lippman SM, Spitz MR, Taylor PR, Klein EA, Thompson IM, Goodman P, Stanford JL, Crowley JJ, Coltman CA, Santella RM. Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Causes Control. 2001 Sep;12(7):627-33.
• El-Bayoumy K. The negative results of the SELECT study do not necessarily discredit the selenium-cancer prevention hypothesis. Nutr Cancer. 2009;61(3):285-6. No abstract available.
• Cook ED, Moody-Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, Lippman SM, Minasian LM, Paskett ED, Craine S, Arnold KB, Probstfield JL. Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Clin Trials. 2005;2(5):436-42.
• Kristal AR, King IB, Albanes D, Pollak MN, Stanzyk FZ, Santella RM, Hoque A. Centralized blood processing for the selenium and vitamin E cancer prevention trial: effects of delayed processing on carotenoids, tocopherols, insulin-like growth factor-I, insulin-like growth factor binding protein 3, steroid hormones, and lymphocyte viability. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):727-30.
• Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM Jr, Kristal AR, Santella RM, Probstfield JL, Moinpour CM, Albanes D, Taylor PR, Minasian LM, Hoque A, Thomas SM, Crowley JJ, Gaziano JM, Stanford JL, Cook ED, Fleshner NE, Lieber MM, Walther PJ, Khuri FR, Karp DD, Schwartz GG, Ford LG, Coltman CA Jr. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst. 2005 Jan 19;97(2):94-102.

DISEASE CHARACTERISTICS:

• Healthy male volunteers

• Digital rectal examination (DRE) deemed not suspicious for prostate cancer performed within 364 days prior to study entry

  • Participants with a suspicious DRE are ineligible even if a recent or subsequent biopsy is negative for cancer
• Total prostate-specific antigen ≤ 4.0 ng/mL within 364 days prior to study entry
• No prior prostate cancer or high-grade (grade 2-3) prostatic intraepithelial neoplasia

PATIENT CHARACTERISTICS:

Age:

• See Disease Characteristics

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• Systolic blood pressure < 160 mm Hg
• Diastolic blood pressure < 90 mm Hg
• No history of hemorrhagic stroke

Other:

• No malignancies within the past 5 years except basal cell or squamous cell skin cancer
• No uncontrolled medical illness
• No retinitis pigmentosa

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 7 years since prior randomization to SWOG-9217, with completion of end-of-study biopsy requirement
• No additional concurrent selenium or vitamin E (contained in individual supplements, antioxidant mix, or multivitamin)
• Concurrent multivitamins allowed (supplied on study)
• No concurrent anticoagulation therapy (e.g., warfarin)

• Concurrent prophylactic aspirin (average daily dose no greater than 175 mg/day) allowed

  • Concurrent daily aspirin dose ≤ 81 mg for participants receiving clopidrogel
• Concurrent anti-hypertension medication allowed
• No concurrent participation in another study involving a medical, surgical, nutritional, or life-style intervention (unless no longer receiving the intervention and are in the follow-up phase only)

• National Cancer Institute (NCI)
• National Center for Complementary and Alternative Medicine (NCCAM)
• Eastern Cooperative Oncology Group
• Cancer and Leukemia Group B
• NCIC Clinical Trials Group