Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy

Clin Cancer Res. 2002 Sep;8(9):2775-81.

Abstract

Purpose: A prospective Phase II study of a novel maintenance biotherapy regimen after induction biochemotherapy was conducted in patients with metastatic melanoma in efforts to maintain responses and improve survival.

Experimental design: Thirty-three patients with poor prognosis metastatic melanoma who achieved a partial response (PR) or stable disease (SD) to induction concurrent biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor, and intermittent pulses of intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of these patients was compared with a control group of patients at our institution who were treated recently with induction biochemotherapy and achieved a PR or SD.

Results: Five patients (15%) achieved a complete response, and 4 patients (12%) maintained SD for at least 6 months on maintenance biotherapy. The median progression-free survival (PFS) and overall survival (OS) were 8.1 months and 18.5 months, respectively, compared with historical controls, which were PFS 5.9 months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P = 0.0001) in multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy regimen was well tolerated with no dose-limiting acute or cumulative toxicities.

Conclusion: In this single institution study, maintenance biotherapy with IL-2 and granulocyte macrophage colony-stimulating factor in patients achieving PR or SD to induction biochemotherapy improved PFS and OS compared with historical controls. A larger multicenter Phase II trial has been initiated in an effort to confirm these results.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Eruptions / etiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Hyperthyroidism / chemically induced
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use*
  • Life Tables
  • Melanoma / drug therapy
  • Melanoma / mortality
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Metastasis
  • Prospective Studies
  • Remission Induction
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vinblastine / administration & dosage

Substances

  • Immunologic Factors
  • Interleukin-2
  • Tamoxifen
  • Vinblastine
  • Dacarbazine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cisplatin