Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597

J Clin Oncol. 2013 Nov 20;31(33):4179-87. doi: 10.1200/JCO.2013.49.2173. Epub 2013 Sep 3.

Abstract

Purpose: Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation.

Patients and methods: Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence.

Results: The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected.

Conclusion: Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alopecia / chemically induced
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / prevention & control*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Chemoprevention / methods
  • Constipation / chemically induced
  • Dietary Supplements*
  • Double-Blind Method
  • Fatigue / chemically induced
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Postoperative Period
  • Selenium / administration & dosage*
  • Selenium / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Selenium