**6. Sunitinib**

Sunitinib is an oral drug with inhibitory activity against several related protein tyrosine kinase receptors, including the platelet-derived growth factor receptor (PDGFR)–ß, stem cell factor receptor (KIT), and Fms-like tyrosine kinase-3, as well as the vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, [13]. Two initial phase II trials of sunitinib 50 mg/day for 4 weeks followed by 2 weeks rest in 169 metastatic renal cell carcinoma (RCC) patients who had failed previous cytokine-based therapy demonstrated an investigator-assessed objective response rate of 45%, a median duration of response of 11.9 months, and a median progression-free survival (PFS) of 8.4 months [14, 15]. Recently, a survival analysis of these patients was reported, suggesting a trend for improved median overall survival (OS) with sunitinib therapy (26.4 vs 21.8 months; hazard ratio: 0.821; 95% confidence interval: 0.673-1.001; P =.051.Based on these data, sunitinib has emerged as a frontline standard of care for patients with metastatic RCC. Common toxicities associated with sunitinib have included fatigue, hand-foot syndrome, diarrhea, mucositis, hypertension and hypothyroidism. Cardiotoxicity has been reported and thus monitoring may be required in patients with preexisting heart disease [16].

In a population-based retrospective analysis comparing patients treated in the IFN era (n=131) versus those treated in the sunitinib era (n=69), the patients treated with first-line sunitinib had an associated doubling in OS compared to those treated with interferon (17.3 versus 8.7 months, p=0.004) [17]. When adjusted for Memorial Sloan Kettering Cancer Center (MSKCC) prognostic criteria, the HR of death for sunitinib versus IFN was 0.049 (p=0.001). Even those patients classified as having a poor prognosis by MSKCC criteria had a survival advantage. Current treatment algorithm for patients with met (10.7 versus 4.1 months, p=0.0329), sug‐ gesting that use of sunitinib is beneficial in this population as well.
