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

• Type of Material: Article
• Authors: Daniel D. Karp, University of Texas MD Anderson Cancer Center; Sandra J. Lee, Dana Farber Cancer Institute; Steven M. Keller, Montefiore Medical Center; Gail Shaw Wright, Florida Cancer Specialists; Seena Aisner, University of Medicine and Dentistry of New Jersey; Steven Alan Belinsky, Lovelace Respiratory Research Institute; David H. Johnson, University of Texas Southwestern; Michael R. Johnston, Dalhousie University; Gary Goodman, Swedish Medical Center; Gerald Clamon, University of Iowa; Gordon Okawara, McMaster University; Randolph Marks, Mayo Clinic; Eric Frechette, Hopital Laval; Worta McCaskill-Stevens, National Cancer Institute; Scott M. Lippman, University of California San Diego; John Ruckdeschel, Intermountain Healthcare; Fadlo Khuri, Emory University
• Language: English
• Date: 2013-11-20
• Publisher: AMER SOC CLINICAL ONCOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2013 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2013.49.2173
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 31
• Issue: 33
• Start Page: 4179
• End Page: +
• Grant/Funding Information: Supported in part by Public Health Service Grants No. CA037403, CA14958, CA80775, CA73590, CA107868, CA49957, CA31946, CA33601, CA32102, CA20319, CA25224, CA21661, and CA37422 and grants from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services.
• Keywords: ISOTRETINOIN; BETA-CAROTENE; Science & Technology; CARDIOVASCULAR-DISEASE; Oncology; Life Sciences & Biomedicine; FORMER SMOKERS; VITAMIN-A; 2ND PRIMARY TUMORS; NECK-CANCER; RISK; BRONCHIAL SQUAMOUS METAPLASIA; PREVENTION
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

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 <g 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.