title: Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  The Cytokine Working Group conducted a randomized phase III trial to determine the value of outpatient interleukin-2 (IL-2) and interferon alfa-2b (IFN) relative to high-dose (HD) IL-2 in patients with metastatic renal cell carcinoma.
  
  
  METHODS
  Patients were stratified for bone and liver metastases, primary tumor in place, and Eastern Cooperative Oncology Group performance status 0 or 1 and then randomly assigned to receive either IL-2 (5 MIU/m(2) subcutaneously every 8 hours for three doses on day 1, then daily 5 days/wk for 4 weeks) and IFN (5 MIU/m(2) subcutaneously three times per week for 4 weeks) every 6 weeks or HD IL-2 (600,000 U/kg/dose intravenously every 8 hours on days 1 through 5 and 15 to 19 [maximum 28 doses]) every 12 weeks.
  
  
  RESULTS
  One hundred ninety-two patients were enrolled between April 1997 and July 2000. Toxicities were as anticipated for these regimens. The response rate was 23.2% (22 of 95 patients) for HD IL-2 versus 9.9% (nine of 91 patients) for IL-2/IFN (P = .018). Ten patients receiving HD IL-2 were progression-free at 3 years versus three patients receiving IL-2 and IFN (P = .082). The median response durations were 24 and 15 [corrected] months (P = .18) [corrected] and median survivals were 17.5 and 13 months (P = .24). For patients with bone or liver metastases (P = .001) or a primary tumor in place (P = .040), survival was superior with HD IL-2.
  
  
  CONCLUSIONS
  This randomized phase III trial provides additional evidence that HD IL-2 should remain the preferred therapy for selected patients with metastatic renal cell carcinoma.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, E/KS-153, Boston, MA 02215, USA. dmcdermo@bidmc.harvard.edu
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Flaherty
authors.forename: Geoffery R
authors.initials: GR
authors.lastname: Weiss
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Logan
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: Christopher P G
authors.initials: CP
authors.lastname: Tretter
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: John W
authors.initials: JW
authors.lastname: Smith
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: James W
authors.initials: JW
authors.lastname: Mier
authors.forename: Jared A
authors.initials: JA
authors.lastname: Gollob
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins