A phase II study of paclitaxel and capecitabine combination chemotherapy in patients with advanced gastric cancer as a first-line therapy

Abstract

4051 Background: Paclitaxel and capecitabine, which have distinct mechanisms of action and toxicity profiles, showed considerable single-agent activity in gastric cancer. Synergistic interaction between these two drugs was also suggested by taxane-induced upregulation of thymidine phosphorylase. Therefore, we evaluated antitumor activity and toxicities of paclitaxel and capecitabine combination in patients with advanced gastric cancer (AGC) as a first-line therapy. Methods: Patients with histologically confirmed AGC with unresectable or metastatic diseases, measurable lesions, PS 0–2, age between 18 and 75, and no contraindication to chemotherapy were eligible in this study. Prior adjuvant chemotherapy finished at least 6 months before enrollment was allowed. Treatment included capecitabine 825 mg/m2 p.o. twice daily on days 1–14 and paclitaxel 175 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities. Results: Between June 2002 and December 2003, total 40 pts were enrolled in this study. The median age was 57.5 years (range, 38–73). Twenty-nine pts were male. Nine pts had recurrent disease after previous curative gastrectomy and 8 had previous adjuvant chemotherapy. After a median 4 (range, 1–9) cycles of chemotherapy, thirty-four pts were evaluable for toxicity and 33 pts for response (6 pts too early for evaluation, 1 pt loss to follow-up). In intention-to-treat analysis, the overall response rate was 52.9% (95% C.I., 36.2–69.6%), including 0 CR, 18 PRs, 9 SDs, and 6 PDs. After a median follow-up of 8.6 months (range, 0.9–17.9), median time to progression was 5.3 months (95% C.I., 3.6–6.9) and median overall survival was 14.6 months (95% C.I., 8.5–20.7). The actual dose intensity was well maintained over 95% of planned during the first 4 cycles in both drugs. Commonly observed grade 3/4 adverse events were neutropenia (41.1% of patients), hand-foot syndrome (11.8%), arthralgia (8.8%). There was no neutropenic fever or treatment-related death. Conclusions:Paclitaxel and capecitabine combination chemotherapy was active and highly tolerable as a first-line therapy for AGC. No significant financial relationships to disclose.