Abstract
PURPOSE: We assessed the clinical activity and safety of gemcitabine plus capecitabine in patients with metastatic renal cell cancer previously treated with immunotherapy. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.