Phase 2 Trial of Capecitabine, Gemcitabine, and Bevacizumab in Sarcomatoid Renal-Cell Carcinoma.

BACKGROUND

Patients with sarcomatoid renal-cell carcinomas (sRCC) have poor outcomes and limited treatment options. Preclinical and clinical data suggest susceptibility to cytotoxic agents and vascular endothelial growth factor-targeted therapies. We designed a phase 2 trial to evaluate the efficacy and safety of capecitabine, gemcitabine, and bevacizumab in sRCC.

PATIENTS AND METHODS

Patients with metastatic or unresectable sRCC were eligible for inclusion. Patients received oral capecitabine 800 mg/m twice daily on days 1 to 21 of a 28-day cycle, intravenous gemcitabine 900 mg/m on days 1 and 15, and intravenous bevacizumab 10 mg/kg on days 1 and 15. Primary end points were progression-free survival and time to treatment failure (TTF). Secondary end points were safety, objective response rate, and overall survival.

RESULTS

Thirty-four patients were enrolled onto the trial. One patient was excluded from survival analysis and 4 from response analysis as a result of missing data. Median progression-free survival was 5.5 months (95% confidence interval [CI], 3.4-7.7), median TTF was 4.2 months (95% CI, 2.4-6.0), and median overall survival was 12 months (95% CI, 10.6-13.4). Objective response rate was 20% (5 partial responses, 1 complete response), and disease control rate was 73%. Thirty-one (91%) of the 34 patients discontinued treatment. The most common reason for treatment discontinuation was progressive disease, which occurred in 24 patients (71%). The most common grade 3 toxicity was rash (including hand-foot syndrome) in 24% patients.

CONCLUSION

The combination of capecitabine, gemcitabine, and bevacizumab is an option for patients with sRCC; however, response rates are low. Novel therapies are needed to improve outcomes in patients with sRCC.