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Clinical Pharmacology

Selected Combination Therapy with Sorafenib: A Review of Clinical Data and Perspectives in Advanced Solid Tumors

Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium

Key Words. Sorafenib • Combination • Solid tumors • Hepatocellular carcinoma • Renal cell carcinoma

Correspondence: Ahmad Awada, M.D., Ph.D., Head of the Medical Oncology Clinic, Jules Bordet Institute, Boulevard de Waterloo 121, B-1000 Brussels, Belgium. Telephone: 32-2-541-3189; Fax: 32-2-538-0858; e-mail: ahmad.awada{at}bordet.be

Received November 28, 2007; accepted for publication June 6, 2008; first published online in THE ONCOLOGIST Express on August 11, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers of the article.

The development of targeted therapies has provided new options for the management of patients with advanced solid tumors. There has been particular interest in agents that target the mitogen-activated protein kinase pathway, which controls tumor growth and survival and promotes angiogenesis. Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in renal cell carcinoma, and there is a strong rationale for investigating its use in combination with other agents. In particular, targeting multiple Raf isoforms with sorafenib may help to overcome resistance to other agents, while the ability of sorafenib to induce apoptosis may increase the cytotoxicity of chemotherapeutic agents. Based on positive results in preclinical studies, further investigation in phase I and II studies has shown potential antitumor activity when sorafenib is combined with cytotoxic agents in different solid tumors, including hepatocellular carcinoma and melanoma. Promising results have been reported in phase I and II studies of sorafenib combined with paclitaxel and carboplatin, with oxaliplatin in gastric and colorectal cancer, with docetaxel in breast cancer, with gemcitabine in ovarian cancer, and with capecitabine in different solid tumors. Phase II and III studies are currently investigating the use of sorafenib in combination with different agents in a variety of solid tumors. The primary objective of this review is to summarize the early clinical studies of sorafenib with cytotoxic agents and discuss future perspectives of these combinations in different tumor types.