Randomized dose-escalation study evaluating peginterferon alfa-2a in patients with metastatic malignant melanoma.
OBJECTIVE
A pegylated interferon, peginterferon alfa-2a (PEG-IFNalpha-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNalpha. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNalpha-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system).


METHODS
PEG-IFNalpha-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 mug (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR).


RESULTS
The major response rate (CR or PR) was 6% in the 180-mug group (CR, 2%; PR, 4%), 8% in the 360-mug group (CR, 2%; PR, 6%), and 12% in the 450-mug group (CR, 6%; PR, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFNalpha-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-mug groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea.


CONCLUSIONS
PEG-IFNalpha-2a at doses up to 450 mug once weekly has shown good tolerability and similar efficacy to conventional IFNalpha and monochemotherapy in stage IV metastatic melanoma.
Dummer
Reinhard
R
Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland. reinhard.dummer@usz.ch
Garbe
Claus
C
Thompson
John A
JA
Eggermont
Alexander M
AM
Yoo
Kisook
K
Maier
Tanja
T
Bergstrom
Bengt
B
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D018450:Disease Progression; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects*; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a