title: Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer.
abstract: OBJECTIVE
  This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens.
  
  
  METHODS
  Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned.
  
  
  RESULTS
  A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04).
  
  
  CONCLUSIONS
  Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.
authors.affiliation: Surgery Branch, Biostatistics and Data Management Section, Department of Pathology, National Cancer Institute/NIH, Room 2B-37, Building 10, 9000 Rockville Pike, Bethesda, MD 20892, USA. james_yang@nih.gov
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Schwartzentruber
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Seipp
authors.forename: Linda
authors.initials: L
authors.lastname: Rogers-Freezer
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Morton
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D007376:Interleukin-2