T K Eigentler1, R Gutzmer2, A Hauschild3, L Heinzerling4, D Schadendorf5, D Nashan6, E Hölzle7, F Kiecker8, J Becker5, C Sunderkötter9, I Moll10, E Richtig11, I Pönitzsch12, H Pehamberger13, R Kaufmann14, C Pföhler15, T Vogt15, C Berking16, M Praxmarer17, C Garbe18. 1. Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen thomas.eigentler@med.uni-tuebingen.de. 2. Department of Dermatology and Allergy, Hannover Medical School, Hannover. 3. Department of Dermatology, University Hospital Kiel, Kiel. 4. Department of Dermatology, University Hospital Erlangen, Erlangen. 5. Department of Dermatology, University Essen-Duisburg, Essen. 6. Department of Dermatology, Hospital Dortmund, Dortmund. 7. Department of Dermatology, Hospital Oldenburg, Oldenburg. 8. Department of Dermatology, Charité Berlin, Berlin. 9. Department of Dermatology, University Hospital Münster, Münster. 10. Department of Dermatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 11. Department of Dermatology, University Hospital Graz, Graz, Austria. 12. Department of Dermatology, University Hospital Leipzig, Leipzig, Germany. 13. Department of Dermatology, AKH Wien, University Hospital Vienna, Vienna, Austria. 14. Department of Dermatology, University Hospital Frankfurt am Main, Frankfurt/Main. 15. Department of Dermatology, Saarland University Medical School, Homburg/Saar. 16. Department of Dermatology and Allergy, University Hospital of Munich, Munich, Germany. 17. Assign Group, Innsbruck, Austria. 18. Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION:PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.
RCT Entities:
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.
Authors: Marisa Boff Costa; Paulo Dornelles Picon; Guilherme Becker Sander; Hugo Nodarse Cuni; Carmen Valenzuela Silva; Rolando Páez Meireles; Ana Carolina Magalhães Andrade Góes; Nadia Maria Batoreu; Maria de Lourdes de Sousa Maia; Elizabeth Maciel Albuquerque; Denise Cristina de Souza Matos; Pedro Lopez Saura Journal: BMC Pharmacol Toxicol Date: 2018-01-04 Impact factor: 2.483