A phase II study of weekly paclitaxel and doxifluridine (an intermediate metabolite of capecitabine) combination chemotherapy for advanced/recurrent gastric cancer

Abstract

4593 Background: Paclitaxel and doxifluridine (5’-DFUR; an intermediate metabolite of capecitabine), which have distinct mechanisms of action and toxicity profiles, each have considerable single-agent activity in gastric cancer. A synergistic interaction between these two drugs was suggested from the taxane-induced upregulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. Therefore, this study evaluated the antitumor activity and toxicities of paclitaxel and 5’-DFUR in combination in patients with advanced/recurrent gastric cancer (AGC) Methods: Patients with histologically confirmed AGC, which was unresectable or metastatic, PS 0–2, and over 20 years old were eligible for this study. The treatment included paclitaxel 80 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and doxifluridine 533 mg/m2 p.o. on days 1–5/week until there was disease progression or the appearance of unacceptable toxicity. Results: Between April 2003 and May 2006,104 patients were enrolled in this study. Their median age was 67.0 years (range: 36–82) and 87 patients were male. Forty-three patients had advanced gastric cancer and 61 had recurrent gastric cancer. After a median of 3 (range: 1- 21) cycles of chemotherapy, 104 patients were evaluated for toxicity and 93 patients were evaluated for response. In the intention-to-treat analysis, the overall response rate was 32.3% (95% C.I., 22.8–41.8%), including 2 CR, 28 PRs, 37 SDs, 16 PDs, and 10 NEs. The first-line therapy involved 48 patients (primary advanced or surgery alone) in whom the response rate was 41.7% (95% C.I., 27.7–55.6%). The second-line therapy involved 40 patients (72.5% TS-1 failure) in whom the response rate was 22.5% (95% C.I., 9.6–35.4%). The median overall survival was 287 days. The actual dose intensity was 81.7% (85/104) of the planned dose during the first two cycles for both drugs. Commonly observed grade 3/4 adverse events were leukopenia (13.5%), anorexia (3.8%), fatigue (3.8%), and diarrhea (2.9%).There was no neutropenic fever or treatment-related death. Conclusions: These data suggest that Paclitaxel and 5’-DFUR combination chemotherapy is a well tolerated convenient out-patient combination with very promising efficacy for AGC. No significant financial relationships to disclose.