Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma.
PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.
Department of Dermatology, University Hospital of Schleswig-Holstein, Campus Kiel, Schittenhelmstr 7, D-24105 Kiel, Germany. ahauschild@dermatology.uni-kiel.de
Axel
A
Hauschild
Michael
M
Weichenthal
Knuth
K
Rass
Ruthild
R
Linse
Jens
J
Ulrich
Rudolf
R
Stadler
Matthias
M
Volkenandt
Stephan
S
Grabbe
Ulrike
U
Proske
Dirk
D
Schadendorf
Norbert
N
Brockmeyer
Thomas
T
Vogt
Rainer
R
Rompel
Roland
R
Kaufmann
Martin
M
Kaatz
Helmut
H
Näher
Peter
P
Mohr
Thomas
T
Eigentler
Elisabeth
E
Livingstone
Claus
C
Garbe
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D055104:Infusions, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy; D055815:Young Adult
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins