A phase II trial of gemcitabine, capecitabine, and bevacizumab in metastatic renal carcinoma.

Objectives: Renal cancer is resistant to most DNA and DNA repair targeted chemotherapy; although moderate response rates to nucleotide analog based therapy have been reported. Bevacizumab also has activity. We thus performed a phase II trial of gemcitabine, capecitabine, and bevacizumab in patients with metastatic renal cancer.

Methods: Following significant hematotoxicity, dosing was modified to gemcitabine 1000 mg/m (Days 1, 8), capecitabine 1000 mg twice daily (Days 1-14), and bevacizumab 15 mg/kg (Day 1) on a 21-day cycle with evaluation every 3 cycles. Primary end point was objective response rate.

Results: Twenty-nine patients were enrolled between March 2005 and May 2008. Most patients had been previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Seven patients (24%) had a partial response. Median overall and progression-free survival were 9.8 months (95% confidence interval: 6.2, 14.9) and 5.3 months (95% confidence interval: 3.9, 9.9), respectively. The regimen was well tolerated with hematologic toxicity, fatigue, and rash being most common.

Conclusion: The trial was terminated early despite not meeting criteria for success or futility because of slow accrual and because the historical response rate became irrelevant with emerging data using sequential vascular endothelial growth factor therapies. Nevertheless, the observed progression-free and overall survival compare favorably to other phase II trials in this heavily pretreated population.