Dose-escalating study of capecitabine plus gemcitabine combination therapy in patients with advanced cancer

Purpose: The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination. Patients and Methods: Eligible patients had advanced solid tumors that had failed to respond to standard therapy or for which no standard therapy was available, measurable or assessable disease, Karnofsky performance status greater than or equal to 70%, and acceptable organ function. Capecitabine was administered twice daily by mouth each day for 21 consecutive days followed by a 1-week break. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break. Results: Forty patients were enrolled onto the study, and 33 are fully assessable for toxicity. The most common toxicities during the first cycle of chemotherapy were neutropenia and mucositis. Only one patient treated at gemcitabine and capecitabine doses of 800 and 2000 mg/m(2), respectively, met protocol-specified DLT criteria; however, at these doses 65% of successive cycles required dose reduction or delay for toxicity. No episodes of DLT were observed at gemcitabine and capecitabine doses of 1,000 and 1,660 mg/m(2), respectively, and 70% of cycles of therapy were delivered without dose reduction or delay. Therefore, these doses are recommended for further study. Tumor responses were observed in patients with metastatic colorectal and pancreatic cancer. Conclusion: Gemcitabine and capecitabine can be combined with acceptable toxicity at nearly full doses. Antitumor activity of the combination merits further investigation in phase 11 studies. (C) 2002 by American Society of Clinical Oncology.