Medical treatment of advanced renal cell carcinoma: Present options and future directions

Objectives: This paper reviews the status of the art concerning medical treatment of advanced renal cell cancer (RCC) and new therapeutic options, namely, targeted therapies. Methods: The review was based on the most recent and relevant papers appearing in the literature. Results: Cytokines, including interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) represent the treatment of choice for most RCC patients. High-dose IL-2 provides a limited but clinically relevant proportion of patients with durable response benefit. Although hormone therapy has only historical value, cytotoxic chemotherapy is an option for patients who become refractory to immunotherapies. Results achieved with cytotoxic drugs are usually poor, though 5-fluororacil, capecitabine, and gemcitabine have moderate activity coupled with manageable toxicity. Growing understanding of RCC biology has provided new targets for biologic therapies. Antiangiogenic drugs, which include monoclonal antibodies against vascular endothelial growth factor (VEGF), such as bevacizumab, or small molecules targeting VEGF receptors, such as SU011248, PTK787/2K22254, and BAY 43-9006, look promising, either alone or in combination with cytokines or cytotoxic drugs. Conclusions: The management of patients with metastatic RCC is still frustrating because the most of these patients die of their disease. Although a limited subset of patients can experience clinically meaningful benefit from IL-2 or IFN-alpha therapy and a limited benefit, if any, can be achieved in these patients with conventional chemotherapy, there is no other proven effective therapy for patients who do not respond or who relapse after cytokine-based treatment. Better understanding of RCC biology has provided insights on relevant signal transduction pathways, genetic mutations, and tumour susceptibilities to innate immune response resulting in novel treatment strategies that promise to affect the natural history of this lethal disease. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.