Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with oral S-1 for advanced gastric cancer with macroscopic peritoneal metastasis.

Abstract

e14530 Background: This phase II study was performed to evaluate the efficacy and the tolerability of weekly intravenous and intraperitoneal paclitaxel (PTX) combined with oral S-1 in gastric cancer patients with macroscopic peritoneal metastasis. We previously reported a phase I and II study with the same regimen in gastric cancer patients with peritoneal metastasis, including patients with positive peritoneal washing cytology but negative macroscopic peritoneal metastasis. This trial was scrutinized and approved by a committee appointed by the Ministry of Health, Labour, and Welfare in Japan and performed under the special interim system for Advanced Medical Technology so as to generate an evidence for future approval of the treatment by the Ministry. Methods: Gastric cancer patients with primary tumors with macroscopic peritoneal metastasis confirmed by staging laparoscopy were enrolled. PTX was administered intravenously at 50 mg/m2, and intraperitoneally through a subcutaneous implanted access port at 20 mg/m2 on days 1 and 8. S-1 was administered orally twice daily at 80 mg/m2/day for 14 consecutive days followed by 7 days rest, repeated every 3 weeks. The primary endpoint was the one-year overall survival rate. Secondary endpoints were the response rate, efficacy against malignant ascites and safety. Results: In total, 35 patients were enrolled. All patients had several to numerous metastases to the distant peritoneum. The median number of administration course was 11 (range 2-29). The one-year overall survival rate was 77.1%. Massive malignant ascites decreased in 6 of 9 (66.7%) patients. Peritoneal washing cytology turned negative in 28 of 29 (96.7%) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 34% and 9%, respectively, all of which were reversible. Grade 3/4 toxicity was observed for neutropenia (34%), leukopenia (23%), anemia (9%). There were no treatment-related deaths. Conclusions: The combination chemotherapy regimen of weekly intravenous and intraperitoneal PTX combined with oral S-1 was well tolerated and active in gastric cancer patients with macroscopic peritoneal metastasis.