Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab

摘要: BACKGROUND: Bevacizumab and sunitinib are standard initial therapy in metastatic renal cell carcinoma (mRCC). Despite common use, the safety activity of sorafenib bevacizumab- or sunitinib-refractory mRCC have not been prospectively investigated. METHODS: Metastatic RCC patients with Response Evaluation Criteria Solid Tumors (RECIST)-defined disease progression (PD) after treatment either bevacizumab received twice daily 400 mg a multicenter, prospective phase 2 study. Dose escalation was permitted absence significant toxicity. The primary endpoint tumor burden reduction rate, defined as proportion ≥5% sum RECIST-defined target lesions without other PD. Secondary endpoints included progression-free survival (PFS), duration response, overall survival, safety. A 2-stage accrual design used to test alternative hypothesis that rate >20% versus <5%. RESULTS: Forty-eight were enrolled. 30% (95% confidence interval [CI], 17%-45%). One unconfirmed objective partial response observed. median PFS 4.4 months CI, 3.6-5.9). There no association shrinkage prior therapy. Most treatment-related adverse events mild-to-moderate intensity, fatigue, hypertension, diarrhea, palmoplantar erythrodysesthesia (PPE). Patients previously treated tended develop more PPE (P = .03) mucositis .06), whereas sunitinib-treated skin rash .06). CONCLUSIONS: Administration is safe feasible refractory sunitinib. Modest clinical observed supporting current practice patterns sequential vascular endothelial growth factor-targeted mRCC. Cancer 2010. © 2010 American Society.