A phase II trial of gemcitabine plus capecitabine for metastatic renal cell cancer previously treated with immunotherapy and targeted agents.

Abstract

We assessed the clinical activity and safety of gemcitabine plus capecitabine in patients with metastatic renal cell cancer previously treated with immunotherapy. In this phase II trial patients received 1,000 mg/m(2) gemcitabine intravenously on days 1, 8 and 15, plus 830 mg/m(2) capecitabine orally twice daily on days 1 to 21 of 28-day cycles. The primary end point was progression-free survival time. Secondary end points included overall survival time, objective response rate and toxicity. Of 84 patients enrolled 83 were evaluable for response and toxicity. A total of 65 patients had intermediate or poor risk prognosis. Median progression-free survival and overall survival were 4.6 (95% CI 3.7-7.3) and 17.9 months (95% CI 13.2-23.6), respectively. There were 6 partial responses and 1 complete response (objective response rate 8.4% [95% CI 3.5-16.6]). Two patients remain in unmaintained remission close to 3 years from the initiation of gemcitabine plus capecitabine treatment. On multivariate analysis more than 3 disease sites were significantly associated with shorter progression-free survival and patients with thrombocytosis, more than 3 disease sites or anemia had a significantly increased risk of death. Adverse events occurring at least once in more than 5% of patients included grade 3 or greater neutropenia (83%), grade 2 or greater hand-foot syndrome (13%), grade 3 or greater thrombocytopenia (12%), grade 3 or greater thromboembolic events (8%), grade 3 or greater fatigue (8%) and grade 2 or greater mucositis (6%). At the doses and schedule tested gemcitabine plus capecitabine demonstrated modest clinical activity in metastatic renal cell cancer after cytokine failure and produced significant neutropenia. A modified gemcitabine plus capecitabine regimen may be evaluated in patients with metastatic renal cell cancer after failure of approved targeted therapies.