Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.
Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS.



In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 μg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability.



A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains.



PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity.



NCT00204529.
Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen thomas.eigentler@med.uni-tuebingen.de.
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TK
Eigentler
Department of Dermatology and Allergy, Hannover Medical School, Hannover.
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R
Gutzmer
Department of Dermatology, University Hospital Kiel, Kiel.
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A
Hauschild
Department of Dermatology, University Hospital Erlangen, Erlangen.
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L
Heinzerling
Department of Dermatology, University Essen-Duisburg, Essen.
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D
Schadendorf
Department of Dermatology, Hospital Dortmund, Dortmund.
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D
Nashan
Department of Dermatology, Hospital Oldenburg, Oldenburg.
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E
Hölzle
Department of Dermatology, Charité Berlin, Berlin.
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F
Kiecker
Department of Dermatology, University Essen-Duisburg, Essen.
J
J
Becker
Department of Dermatology, University Hospital Münster, Münster.
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C
Sunderkötter
Department of Dermatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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I
Moll
Department of Dermatology, University Hospital Graz, Graz, Austria.
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E
Richtig
Department of Dermatology, University Hospital Leipzig, Leipzig, Germany.
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I
Pönitzsch
Department of Dermatology, AKH Wien, University Hospital Vienna, Vienna, Austria.
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H
Pehamberger
Department of Dermatology, University Hospital Frankfurt am Main, Frankfurt/Main.
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R
Kaufmann
Department of Dermatology, Saarland University Medical School, Homburg/Saar.
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C
Pföhler
Department of Dermatology, Saarland University Medical School, Homburg/Saar.
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T
Vogt
Department of Dermatology and Allergy, University Hospital of Munich, Munich, Germany.
C
C
Berking
Assign Group, Innsbruck, Austria.
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M
Praxmarer
Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen.
C
C
Garbe
D000293:Adolescent; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
PEG-interferon α-2a; adjuvant drug therapy; interferon α-2a; melanoma; randomized, controlled trial