title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.
authors.affiliation: Daniel D. Karp, The University of Texas MD Anderson Cancer Center, Houston; David H. Johnson, University of Texas Southwestern, Dallas, TX; Sandra J. Lee, Dana-Farber Cancer Institute, Boston, MA; Steven M. Keller, Montefiore Medical Center, Bronx, NY; Gail Shaw Wright, Florida Cancer Specialists, New Port Richey, FL; Seena Aisner, University of Medicine and Dentistry of New Jersey/New Jersey Medical School Cancer Institute of New Jersey, Newark, NJ; Steven Alan Belinsky, Lovelace Respiratory Research Institute, Albuquerque, NM; Gary Goodman, Swedish Medical Center Cancer Institute; Gary Goodman, Fred Hutchinson Cancer Research Center, Seattle, WA; Gerald Clamon, University of Iowa, Iowa City, IA; Randolph Marks, Mayo Clinic, Rochester, MN; Worta McCaskill-Stevens, National Cancer Institute, Rockville, MD; Scott M. Lippman, University of California San Diego Cancer Center, San Diego, CA; John Ruckdeschel, Intermountain Healthcare, Salt Lake City, UT; Fadlo R. Khuri, Emory University, Atlanta, GA; Michael R. Johnston, Dalhousie University, Halifax, Nova Scotia; Michael R. Johnston, National Cancer Institute of Canada Clinical Trials Group, Kingston; Gordon Okawara, McMaster University, Hamilton, Ontario; and Eric Frechette, Hopital Laval, Quebec City, Quebec, Canada.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Karp
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Steven M
authors.initials: SM
authors.lastname: Keller
authors.forename: Gail Shaw
authors.initials: GS
authors.lastname: Wright
authors.forename: Seena
authors.initials: S
authors.lastname: Aisner
authors.forename: Steven Alan
authors.initials: SA
authors.lastname: Belinsky
authors.forename: David H
authors.initials: DH
authors.lastname: Johnson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Johnston
authors.forename: Gary
authors.initials: G
authors.lastname: Goodman
authors.forename: Gerald
authors.initials: G
authors.lastname: Clamon
authors.forename: Gordon
authors.initials: G
authors.lastname: Okawara
authors.forename: Randolph
authors.initials: R
authors.lastname: Marks
authors.forename: Eric
authors.initials: E
authors.lastname: Frechette
authors.forename: Worta
authors.initials: W
authors.lastname: McCaskill-Stevens
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: John
authors.initials: J
authors.lastname: Ruckdeschel
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D018890:Chemoprevention / Q000379:methods; D003248:Constipation / Q000139:chemically induced; D019587:Dietary Supplements; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012643:Selenium / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D012643:Selenium