Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.

Abstract

139 Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m2 (level 1), stepped up to 30 or 40 mg/m2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles. Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m2 and 25 mg/m2, respectively, while keeping the dose of IP PTX at 20 mg/m2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion. Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials. No significant financial relationships to disclose.