Combining Capecitabine and Gemcitabine in Patients With Advanced Pancreatic Carcinoma: A Phase I/II Trial

Purpose: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. Patients and Methods: This multicenter study included patients naïve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m2 on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in ≥ one third of a cohort of six patients. We included an additional 15 patients at the MTD. Results: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m2 bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m2 bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19–9 occurred in 14 of 24 assessable patients. Conclusion: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.