title: 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.
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.
authors.affiliation: Haematologisch-Onkologische Praxis Altona (HOPA), Max-Brauer-Allee 52, D-22765 Hamburg, Germany. urkleeberg@hopa-hamburg.de
authors.forename: U R
authors.initials: UR
authors.lastname: Kleeberg
authors.forename: S
authors.initials: S
authors.lastname: Suciu
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: D J
authors.initials: DJ
authors.lastname: Ruiter
authors.forename: C
authors.initials: C
authors.lastname: Chartier
authors.forename: D
authors.initials: D
authors.lastname: Liénard
authors.forename: J
authors.initials: J
authors.lastname: Marsden
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: A M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D010936:Plant Extracts / Q000627:therapeutic use*; D010940:Plant Proteins / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010936:Plant Extracts; D010940:Plant Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; C077177:viscum album peptide