Sorafenib reveals efficacy in sequential treatment of metastatic renal cell cancer

Abstract

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-α 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 β 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.

Keywords::

• metastatic renal cell cancer
• prognosis
• second line
• sequential therapy
• sorafenib
• targeted therapy
• tyrosine kinase inhibitor

Financial & competing interests disclosure

Markus A Kuczyk is an advisor for Karl Storz, Bayer Schering Pharma, he is an invited speaker for Pfizer, Karl Storz and Bayer Schering Pharma, and is an investor for clinical trials initiated by Pfizer, Bayer Schering Pharma, Wyeth, Novartis and Astra Zeneca. Axel S Merseburger is an advisor for Karl Storz, Bayer Schering Pharma and Ipsen Pharma, and he is an invited speaker for Speciality European Pharma, Wyeth, Roche, and is an investor for clinical trials initiated by Ipsen Pharma, Bayer Schering Pharma and Astra Zeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.