Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma

Background The tyrosine kinase inhibitors(TKIs)sunitinib,the first targeted agent for the first line treatment ofmetastatic renal cell carcinoma(RCC),targets the vascular endothelial growth factor(VEGF)pathway.The objective ofthis study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm ifhypertension is an effective predictive factor.Methods A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010.Amongthem 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy.Thepathology of all patients was confirmed predominant in clear cell type.Sunitinib mono-therapy was administered inrepeated 6-week cycles of daily oral therapy for 4 weeks,followed by 2 weeks off in 34 patients; and 3 patients wereadministered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred.Overall responserate and safety were evaluated.We divided patients into Group A and Group B according to the blood pressure level.Results The median follow-up was 15 months(10 cycles,range 1.5-30.0 months(1-20 cycles)).Ten patients(29.4%)achieved partial responses(PR); 23 patients(67.6%)demonstrated stable disease(SD)lasting >2 cycles.Seventeenpatients(50%)developed progressive disease(PD)during follow-up.The median progression-free survival(PFS)was 15months(range 3.0-28.5)months.A total of 9 patients died; the overall survival has not been reached; the median survivaltime of the deceased patients was 13 months(range 7-24)months.The most common adverse events were hand-footsyndrome(77.8%),thrombocytopenia(75.0%),hypertension(61.1%)and diarrhea(46.0%).Most adverse events werereversible by treatment interruption.Twenty-two patients(61.1%)developed hypertension; and hypertension wasassociated with a long time to disease progression and long overall survival(P=0.004,0.000,respectively).Conclusions The results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as asingle agent in first-or second-line therapy for patients with metastatic clear cell RCC.Further,sunitinib-associatedhypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.