title: Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial.
abstract: OBJECTIVE
  This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC).
  
  
  METHODS
  Eligibility requirements were resected locally advanced (LA; T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history.
  
  
  RESULTS
  Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival.
  
  
  CONCLUSIONS
  One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.
authors.affiliation: Cardinal Bernardin Cancer Center, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. jclark@lumc.edu
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Steven
authors.initials: S
authors.lastname: Creech
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Larry
authors.initials: L
authors.lastname: Flaherty
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Logan
authors.forename: Richard
authors.initials: R
authors.lastname: White
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Weiss
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.forename: Christopher P G
authors.initials: CP
authors.lastname: Tretter
authors.forename: David
authors.initials: D
authors.lastname: McDermott
authors.forename: John W
authors.initials: JW
authors.lastname: Smith
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2