Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group

J Clin Oncol. 2005 Sep 20;23(27):6747-55. doi: 10.1200/JCO.2005.03.202.

Abstract

Background: Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma.

Patients and methods: Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 x 10(6) U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 x 10(6) U/m2/6 hours, 18 x 10(6) U/m2/12 hours, 18 x 10(6) U/m2/24 hours, and 4.5 x 10(6) U/m2 for 3 x 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles.

Results: Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%).

Conclusion: Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy, Needle
  • Cisplatin / therapeutic use
  • Dacarbazine / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Europe
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interleukin-2 / therapeutic use
  • Male
  • Maximum Tolerated Dose
  • Melanoma / drug therapy*
  • Melanoma / mortality*
  • Melanoma / pathology
  • Melanoma / secondary
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Probability
  • Proportional Hazards Models
  • Recombinant Proteins
  • Reference Values
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology*
  • Survival Rate
  • Treatment Outcome

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Interleukin-2
  • Recombinant Proteins
  • Dacarbazine
  • Cisplatin