Final Results of the EORTC 18871/DKG 80-1 Randomised Phase III Trial. rIFN-alpha2b Versus rIFN-gamma Versus ISCADOR M Versus Observation After Surgery in Melanoma Patients With Either High-Risk Primary (Thickness >3 Mm) or Regional Lymph Node Metastasis

Eur J Cancer. 2004 Feb;40(3):390-402. doi: 10.1016/j.ejca.2003.07.004.

Abstract

Between 1988 and 1996, the European Organisation for Research and Treatment of Cancer Melanoma Group (EORTC-MG) performed a prospective, randomised phase III adjuvant trial to evaluate the efficacy and toxicity of low dose recombinant interferon-alpha 2 b (rIFN-alpha2b) (1 MU) or recombinant interferon gamma (rIFN-gamma), (0.2 mg) both given subcutaneously (s.c.), every other day (qod), for 12 months in comparison with an untreated control group. The German Cancer Society (DKG) added a fourth arm with Iscador M, a popular mistletoe extract. High-risk stage II patients (thickness >3 mm) and stage III patients (positive lymph nodes) without distant metastasis were randomised and followed until their first progression or death. An intention-to-treat analysis was performed. From 1988 to 1996, a total of 830 patients were randomised: 423 in the three-arm EORTC 18871 trial and 407 patients in the four-arm DKG 80-1 trial. The median follow-up was 8.2 years and a total of 537 relapses and 475 deaths were reported. At 8 years, the disease-free interval (DFI) rate was 32.4% and the overall survival (OS) rate was 40.0%. In terms of the DFI, the hazard ratio estimates (95% Confidence Intervals (CI)) were: 1.04 (0.84, 1.30) for the comparison of rIFN-alpha2b versus control, 0.96 (0.77, 1.20) for rIFN-gamma versus control, and 1.32 (0.93, 1.87) for Iscador M versus control. In terms of OS, the corresponding estimates (95% CI) for the 3 treatment comparisons were: for IFN-alpha2b 0.96 (0.76, 1.21), for rIFN-gamma 0.87 (0.69, 1.10) and for Iscador M 1.21 (0.84, 1.75), respectively. The results show no clinical benefit for adjuvant treatment with low dose rIFN-alpha2b or rIFN-gamma or with Iscador M in high-risk melanoma patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Feasibility Studies
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / therapeutic use*
  • Lymphatic Metastasis
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Plant Extracts / therapeutic use*
  • Plant Proteins / therapeutic use*
  • Recombinant Proteins
  • Risk Factors
  • Skin Neoplasms / drug therapy*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Plant Extracts
  • Plant Proteins
  • Recombinant Proteins
  • Interferon-gamma
  • viscum album peptide