Tyrosine kinase inhibitors compared with cytokine therapy for metastatic renal cell carcinoma: overview of recent clinical trials differentiating clinical response and adverse effects.

Metastatic renal cell carcinoma has long been recognized as an aggressive, therapy-refractory epithelial cancer. Two decades of clinical experience with the biologic response modifiers, such as interferon and interleukin-2, have produced little in the way of clinically meaningful benefit for patients, with the notable exception of a very small number of patients treated with high-dose interleukin-2. The paradigm shifting development in the understanding of the molecular biology of clear-cell renal cancer and the rapid introduction of kinase inhibitors into our therapeutic armamentarium has provided clinicians and their patients real hope. Two important phase III trials are reviewed and placed into historical context with previous trials of biologic response modifiers.