Sorafenib reveals efficacy in sequential treatment of metastatic renal cell cancer.

Metastatic renal cell carcinoma (mRCC) is a highly vascularized tumor with a generally poor prognosis. It is largely resistant to conventional cancer treatment, including most schemes of hormonal and cytokine therapy as well as to modern chemotherapy. Although IFN-alpha has been the first choice in mRCC treatment strategies for more than a decade, recent recommendations of the European Association of Urology focus on so-called molecular-targeted therapies, with multikinase inhibitors, such as sorafenib and sunitinib, blocking the progression of cell proliferation and tumor angiogenesis, as preferential therapy. Sorafenib targets the VEGF receptor, the PDGF receptor beta and, finally, Raf kinase, and is approved for patients who have either received cytokines or are unsuitable for such a therapy. Although targeted therapies reveal superior efficacy compared with previous cytokine-based approaches, they do not cure patients with metastatic disease. Therefore, following tumor progression, most patients require a second-line or sequential therapy during the further progress of the disease. Owing to the fact that optimal sequencing of these new agents has not been fully elucidated, some recent mainly retrospective studies compared the sequence of sorafenib and sunitinib in order to assess the best clinical benefit in mRCC patients. Apparently, no cross-resistance could be observed in any trial, and most results demonstrated a superior efficacy of a sequence strategy when sorafenib was applied as first-line treatment. Regarding current investigations, the aim of the present article is to address and critically discuss the clinical data concerning the efficacy of sorafenib as part of a sequential treatment of mRCC.