Age-related cataract in men in the selenium and vitamin e cancer prevention trial eye endpoints study: a randomized clinical trial.

IMPORTANCE: Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium. OBJECTIVE: To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. DESIGN, SETTING, AND PARTICIPANTS: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35,533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11,267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study. INTERVENTIONS: Individual supplements of selenium (200 µg per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-α-tocopheryl acetate). MAIN OUTCOMES AND MEASURES: Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract. RESULTS: During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95 % CI, 0.75-1.11; P = .37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95 % CI, 0.84-1.25; P = .81). Similar results were observed for cataract extraction. CONCLUSIONS AND RELEVANCE: These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00784225.

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. OBJECTIVE: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00006392.

Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07.

PURPOSE: The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments. PATIENTS AND METHODS: Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up. RESULTS: A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P < .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, "quite a bit" of cold-induced hand/foot pain 26% FLOX v 2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group. CONCLUSION: Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.

Can complementary and alternative medicine clinical cancer research be successfully accomplished? The Mayo Clinic-North Central Cancer Treatment Group experience.

Some critics question whether research on complementary and alternative modalities for patients with cancer can be done efficiently in traditional clinical settings. This article reviews a program of complementary medicine research that has been done in a traditional clinical setting over the past 30 years. Trials using complementary therapies for both symptom management and cancer treatment done by the Mayo Clinic and the North Central Cancer Treatment Group are reviewed. Twenty-seven studies have been developed using complementary therapies, addressing such issues as mucosal and epidermal toxicity, hot flashes, lymphedema, anorexia and cachexia, insomnia, cognitive dysfunction, fatigue, and cancer treatment. Nineteen of them have been completed and have had results published in peer-reviewed clinical journals, whereas two manuscripts are in press. Two other trials have recently completed accrual, and the data are being analyzed so that manuscripts can be prepared. In addition, four clinical trials are actively accruing patients. The data presented in this article demonstrate that complementary and alternative medicine research can be done in a scientifically sound manner. Well-designed and adequately powered studies can be implemented, and large numbers of patients can be accrued. The resulting research evaluations can be published in peer-reviewed medical journals.