Efficacy of low-dose interferon {alpha}2a 18 versus 60 months of treatment in patients with primary melanoma of >= 1.5 mm tumor thickness: results of a randomized phase III DeCOG trial.
PURPOSE Low-dose (LD) interferon (IFN) alfa (LDI) has demonstrated a consistent disease-free survival benefit for patients with clinically lymph node-negative melanoma in clinical trials. However, the optimal duration of treatment is still under discussion, and no previous trial has evaluated this question specifically. A prolongation of LDI from 18 months to 60 months might be of clinical benefit for patients with intermediate or high-risk melanoma. PATIENTS AND METHODS Eight hundred fifty patients with resected cutaneous melanoma of at least 1.5 mm tumor thickness were included in this prospective randomized, multicenter trial in Germany and Austria. Patients had to be clinically lymph node-negative, and sentinel node biopsy (SLNB) was performed in a majority of cases. They were randomly assigned to receive 3 MU IFNalpha2a three times a week subcutaneously for either 18 months (arm A) or 60 months (arm B). Results Of 850 randomly assigned patients, 840 were eligible for evaluation after a median follow-up of 4.3 years. Tumor thickness and other relevant prognostic factors were well balanced between both groups. SLNB was performed in 635 patients (75.6%), with a positivity rate of 18.0% in arm A and 17.5% in arm B. Neither relapse-free survival (arm A, 75.6% v arm B, 72.6%; P = .72; hazard ratio, 1.05; 95% CI, 0.80 to 1.39) nor distant-metastasis-free survival (81.9% v 79.7%; P = .56; HR, 1.10; 95% CI, 0.80 to 1.52) or overall survival (85.9% v 84.9%; P = .86; HR, 1.03; 95% CI, 0.71 to 1.50) showed significant differences. CONCLUSION A prolongation of conventional LDI therapy from 18 to 60 months showed no clinical benefit in patients with intermediate and high-risk primary melanoma.
Hauschild
Axel
A
Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, D-24105 Kiel. ahauschild@dermatology.uni-kiel.de
Weichenthal
Michael
M
Rass
Knuth
K
Linse
Ruthild
R
Berking
Carola
C
Böttjer
Jörg
J
Vogt
Thomas
T
Spieth
Konstanze
K
Eigentler
Thomas
T
Brockmeyer
Norbert H
NH
Stein
Annette
A
Näher
Helmut
H
Schadendorf
Dirk
D
Mohr
Peter
P
Kaatz
Martin
M
Tronnier
Michael
M
Hein
Rüdiger
R
Schuler
Gerold
G
Egberts
Friederike
F
Garbe
Claus
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001317:Austria; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011994:Recombinant Proteins; D018570:Risk Assessment; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins