A multi-center phase II study of S-1 plus paclitaxel as first-line therapy in patients with advanced or relapsed gastric cancer

4634 Background: S-1 is an oral prodrug of 5-fluorouracil (5-FU) including two modulators to enhance the antitumor effect and to decrease gastrointestinal toxicity. Paclitaxel has the synergistic antitumor effect with 5-FU. This study were planned to evaluate the efficacy and safety of S-1 and paclitaxel combination therapy in advanced gastric cancer. Methods: Eligible patients had untreated advanced or relapsed gastric cancer with measurable lesion(s), histologic proof, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of S-1 35mg/m2 p.o. b.i.d. on days 1–14 plus paclitaxel 70mg/m2 i.v. on days 1& 8 of a 21-day cycle. Measurable and/or unmeasurable lesion was assessed after every 2 courses with RECIST criteria. Results: A total of 56 patients (M/F=37/19) were enrolled. The median age was 59 years with advanced (n=43) and relapsed (n=13) gastric cancer. The common metastatic lesions were abdominal lymph nodes (71%), liver (39%), and peritoneum (21%). Out of 53 evaluable patients, there was 1 (2%) CR, 25 (47%) PRs, 21 (40%) SDs, and 6 (11%) PDs. Objective tumor response was 49%. Median duration of response was 5.4+months after the confirmation of response. Median follow-up was 9.6 month. Median PFS was 7.7 months and median survival was 14.6 months. Median number of cycle was 6 (range, 1–14). The relative dose intensity of S-1 and paclitaxel was 93%, both. The most common causes of delayed cycle and dose reduction were neutropenia and diarrhea, respectively. All 56 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 14%/5%, grade 3 febrile neutropenia in 5%, grade 2/3 N/V in 21%/0%, anorexia in 18%/2%, diarrhea in 9%/4%, stomatitis in 7%/4%, and neuropathy 7%/0% of patients. Conclusions: S-1 and paclitaxel combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with advanced gastric cancer. (This study was partially supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0412-CR01–0704–0001)) No significant financial relationships to disclose.