Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma

J Clin Oncol. 2007 May 20;25(15):2078-85. doi: 10.1200/JCO.2006.10.1709.

Abstract

Purpose: To compare the overall survival (OS) of patients with resected stage III melanoma administered active specific immunotherapy and low-dose interferon alfa-2b (IFN-alpha-2b) with the OS achieved using high-dose IFN-alpha-2b.

Patients and methods: An Ad Hoc Melanoma Working Group of 25 investigators treated 604 patients from April 1997 to January 2003. Patients were stratified by sex and number of nodes and were randomly assigned to receive either 2 years of treatment with active specific immunotherapy with allogeneic melanoma lysates and low-dose IFN-alpha-2b (arm 1) or high-dose IFN-alpha-2b alone for 1 year (arm 2). Active specific immunotherapy was injected subcutaneously (SC) weekly for 4 weeks, at week 8, and bimonthly thereafter. IFN-alpha-2b SC was begun on week 4 and continued thrice weekly at 5 MU/m2 for 2 years. IFN-alpha-2b in arm 2 was administered according to the Eastern Cooperative Oncology Group 1684 study regimen.

Results: Median follow-up time was 32 months for all patients and 42 months for surviving patients. Median OS time exceeds 84 months in arm 1 and is 83 months in arm 2 (P = .56). Five-year OS rate is 61% in arm 1 and 57% in arm 2. Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm 2, with median RFS times of 58 and 50 months, respectively. The incidence of serious adverse events as a result of treatment was the same in both arms, but more severe neuropsychiatric toxicity was seen in arm 2.

Conclusion: OS and RFS achieved by active specific immunotherapy and low-dose IFN-alpha-2b were indistinguishable from those achieved by high-dose IFN-alpha-2b. Long RFS and OS times were observed in both treatment arms.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Combined Modality Therapy
  • Cytoskeletal Proteins
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy, Active*
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Lipid A / analogs & derivatives
  • Lymphatic Metastasis
  • Male
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Recombinant Proteins
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Survival Rate

Substances

  • Cancer Vaccines
  • Cytoskeletal Proteins
  • Drug Combinations
  • Interferon alpha-2
  • Interferon-alpha
  • Lipid A
  • Melacine
  • Recombinant Proteins
  • detox adjuvant