Review Article · Übersichtsarbeit

Metastatic Melanoma: Scientific Rationale for Sorafenib Treatment and Clinical Results
Friederike Egberts, Katharina C. Kähler, Elisabeth Livingstone, Axel Hauschild

Department of Dermatology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany

Address of Corresponding Author

Onkologie 2008;31:398-403 (DOI: 10.1159/000137714)

  Key Words

• Melanoma
• Metastasis
• Sorafenib
• Multikinase inhibitors

  Summary

In advanced metastatic melanoma (AJCC stage IV), the prognosis is still poor, and views differ on the appropriate systemic treatment for these patients. Therefore, new approaches in therapeutic regimens are mandatory. Sorafenib is an oral multikinase inhibitor that targets 2 classes of kinases which are known to be involved in both tumor proliferation and angiogenesis. These kinases include Raf kinases and the vascular endothelial growth factor (VEGF) receptor. Sorafenib has been evaluated as a single therapy agent as well as in combination with various chemotherapeutical drugs in a number of clinical trials. The vast majority of clinical data exists for patients with advanced renal cell cancer for which sorafenib has been approved by the FDA and EMEA. Very recently, sorafenib was approved for advanced hepatocellular cancers due to its overall survival improvement. Since B-raf gene mutations have been found in 69% of melanoma cell lines, sorafenib was brought into various phase I/II and phase III trials in metastatic melanoma. However, as a single-agent therapy, sorafenib seems to be of limited use. Also, the combination of sorafenib with the chemotherapeutic agents carboplatin and paclitaxel has failed to show superiority in progression-free and overall survival compared to the same chemoregimen plus an oral placebo in a phase III trial (PRISM study). More promising data were observed in large-sized phase II studies on dacarbazine (DTIC) plus sorafenib and temozolomide plus sorafenib. However, these data need to be confirmed in prospective randomized phase III trials. Till then, sorafenib remains an interesting but still experimental new agent for melanoma.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Prof. Dr. med. Axel Hauschild, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Universitäts-Hautklinik, Schittenheimstr. 7, 24105 Kiel, Germany, Tel. +49 4315971-613, Fax -853, E-mail ahauschild@dermatology.uni-kiel.de

  Article Information

Published online: June 23, 2008
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 0, Number of References : 0