Update on Prostate Cancer Chemoprevention

Jennifer Fisher Lowe, PharmD; Lawrence A. Frazee, PharmD

Disclosures

Pharmacotherapy. 2006;26(3):353-359. 

In This Article

Nutrients and Vitamins

The role of dietary constituents and vitamins in the chemoprevention of prostate cancer has been addressed in several clinical trials. Substances such as carotenoids (β-carotene and lycopene), vitamin E, and selenium may all affect the development of prostate cancer. Most of the available data consist of epidemiologic or retrospective studies and should be interpreted with attention to potential confounders. The few prospective trials available evaluated prostate cancer as a secondary end point.

Carotenoids

Lycopene and β-carotene are found primarily in fruits such as watermelon and tomatoes.[18] Lycopene is thought to possess significant antioxidant properties that may confer some antineoplastic activity.[19] Two studies evaluated the association between dietary carotenoids and prostate cancer.[20,21] The earliest of these, a prospective cohort study of health care professionals, used a questionnaire to assess the dietary intake of carotenoids in 47,894 subjects.[21] The investigators found that increased lycopene intake was associated with a decreased risk of prostate cancer (relative risk [RR] 0.65, 95% confidence interval [CI] 0.44–0.95) and advanced prostate cancer (RR 0.47, 95% CI 0.22–1.00). The second trial, a case-control study that assessed dietary lycopene and β-carotene intake in 317 men with prostate cancer and 480 healthy men, found a weak inverse association between prostate cancer and intake of lycopene but not β-carotene.[20]

The Physicians Health Study was a randomized, double-blind, placebo-controlled study of aspirin and β-carotene in 22,071 healthy male physicians aged 40–84 years.[22] In a nested case-control study involving men from the Physicians Health Study, plasma levels of antioxidants were measured, and a correlation was found between decreased plasma lycopene concentration and development of prostate cancer.[23] The study involved 578 healthy physicians who developed prostate cancer within 13 years, and 1294 disease-free subjects matched for age and smoking status. The association was strongest in men in the placebo group in the highest quintile of plasma lycopene concentration (odds ratio [OR] 0.40, 95% CI 0.34–0.91, p trend = 0.006 for aggressive cancer).

Another nested case-control study involving men from the Physicians Health Study considered baseline β-carotene plasma concentration and risk of prostate cancer.[24] The investigators found a nonsignificant trend toward increased prostate cancer risk and the lowest quartile of baseline plasma β-carotene concentration in 631 case patients and 2204 controls (OR 1.45, 95% CI 0.98–2.15). Men in the lowest quartile of plasma β-carotene concentration assigned to supplementation with β-carotene 50 mg every other day had a reduced risk of prostate cancer compared with those assigned to placebo (OR 0.68, 95% CI 0.46–0.99). Results from the full Physicians Health Study cohort did not show a reduced risk of prostate cancer with β-carotene supplementation (RR 0.98, 95% CI 0.87–1.11)[22,24]

Finally, the α-tocopherol β-carotene (ATBC) cancer prevention study enrolled 29,133 male cigarette smokers aged 50–69 years to receive α-tocopherol 50 mg, β-carotene 20 mg, α-tocopherol plus β-carotene, or placebo for 5–8 years.[25] This trial reported an increased risk of prostate cancer with β-carotene compared with placebo (138 vs 112 men); however, no statistics were provided.

Vitamin E and Selenium

Vitamin E in the form of α-tocopherol has been evaluated as an antioxidant in several disease states. Its role in preventing prostate cancer was assessed as a secondary end point in the ATBC cancer prevention study, which reported a 34% relative risk reduction (log-rank test, p < 0.01).[25]

Similar to the research with lycopene, several epidemiologic studies have identified an inverse association between selenium concentrations and prostate cancer.[26,27,28] In the Nutritional Prevention of Cancer Study, 1312 patients recruited from low-selenium areas of the eastern United States were randomized to receive high-selenium yeast (equivalent to selenium 200 µg/day) or placebo to prevent recurrence of nonmelanoma skin cancer.[29] After 7.5 years of follow-up, the rate of prostate cancer occurrence (a secondary end point) was significantly reduced (RR 0.51, 95% CI 0.29–0.88). The protective effect of selenium appeared to be most prominent in men with low baseline levels of PSA (< 4 ng/ml) (RR 0.35, 95% CI 0.13–0.87) and low baseline plasma selenium concentrations (RR 0.14, 95% CI 0.02–0.59).

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was started to evaluate the role of vitamin E and selenium supplementation in preventing prostate cancer.[30] This prospective, randomized, double-blind, placebo-controlled prevention trial involves healthy men with a normal digital rectal examination and a serum PSA level below 4 ng/ml. Subjects were randomized to one of four treatment groups: vitamin E (400-mg racemic α-tocopherol) plus selenium (200-µg 1-selenomethionine), vitamin E plus placebo, selenium plus placebo, or placebo plus placebo. A minimum follow-up period of 7 years is planned. Enrollment of patients began in August 2001 and was closed in June 2004 with 35,534 participants; final study results are anticipated in 2013. Unlike trials with selenium and vitamin E reported so far, in which prostate cancer was a secondary end point, clinical diagnosis of prostate cancer is the primary end point of SELECT.

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