Integrated therapy of kidney cancer

Historically, treatment options for metastatic renal cell carcinoma (RCC) have been limited because of inherent tumor resistance to chemotherapy and radiotherapy. The only approved drug for RCC in the past 30 years has been high-dose interleukin-2. Its benefit is observed in a small percentage (20%-25%) of highly selected good performance status RCC patients. The treatment of advanced RCC has recently undergone a major change with the development of potent angiogenesis inhibitors and targeted agents. In fact, advanced RCC is a highly vascular tumor associated with expression of vascular enclothelial growth factor (VEGF); thereafter, antiangiogenic strategies have become an attractive approach. Several multitargeted tyrosine kinase inhibitors (sorafenib and sunitinib) have already been approved for the treatment of advanced RCC; bevacizumab, a monoclonal antibody anti-VEGF, has shown promising clinical activity. Temsrolimus, a derivative of rapamycin (CCI-779), has also shown a survival advantage over interferon in advanced, poor-prognosis RCC patients. The aim of this review is to describe these agents in terms of mechanisms of action, efficacy, and toxicity profile and also to analyze future development strategies.