F Egberts1, R Gutzmer2, S Ugurel3, J C Becker3, U Trefzer4, A Degen2, F Schenck2, L Frey5, T Wilhelm4, J C Hassel6, D Schadendorf7, E Livingstone8, C Mauch9, C Garbe10, C Berking11, K Rass12, P Mohr13, K C Kaehler1, M Weichenthal1, A Hauschild14. 1. Department of Dermatology, University of Kiel, Kiel. 2. Department of Dermatology, Hannover Medical School, Hannover. 3. Department of Dermatology, University of Würzburg, Würzburg, Germany; Department of Dermatology, University of Graz, Graz, Austria. 4. Department of Dermatology, University of Berlin, Berlin. 5. Department of Dermatology, University of Würzburg, Würzburg, Germany. 6. Department of Dermatology, University of Heidelberg-Mannheim, Heidelberg. 7. Department of Dermatology, University of Essen, Essen. 8. Department of Dermatology, University of Kiel, Kiel; Department of Dermatology, University of Essen, Essen. 9. Department of Dermatology, University of Köln, Köln. 10. Department of Dermatology, University of Tübingen, Tübingen. 11. Department of Dermatology, University of Munich, Munich. 12. Department of Dermatology, University of Homburg/Saar, Homburg/Saar. 13. Dermatological Center, Buxtehude, Buxtehude, Germany. 14. Department of Dermatology, University of Kiel, Kiel. Electronic address: ahauschild@dermatology.uni-kiel.de.
Abstract
BACKGROUND: The combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer. PATIENTS AND METHODS: Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 μg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR). RESULTS: Between February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20-85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22-3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms. CONCLUSION: The combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.
BACKGROUND: The combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer. PATIENTS AND METHODS: Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 μg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR). RESULTS: Between February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20-85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22-3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms. CONCLUSION: The combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.
Authors: Ronald S Go; Sandra J Lee; Donghoon Shin; Steven M Callister; Dean A Jobe; Robert M Conry; Ahmad A Tarhini; John M Kirkwood Journal: Clin Cancer Res Date: 2013-10-11 Impact factor: 12.531
Authors: J P Maroto; X G del Muro; B Mellado; J L Perez-Gracia; R Andrés; J Cruz; E Gallardo; M Domenech; J A Arranz; J A Meana Journal: Clin Transl Oncol Date: 2013-01-29 Impact factor: 3.405