BACKGROUND Peritoneal metastasis (PM) remains a major obstacle in the treatment of stage IV gastric cancer. This is a dose-escalation study of intraperitoneal (IP) paclitaxel combined with intravenous (IV) fluorouracil, leucovorin, and oxaliplatin (FOLFOX) to determine the recommended phase II dose in gastric cancer patients.

METHODS Patients with gastric adenocarcinoma and PM were enrolled. The recommended phase II dose of IP paclitaxel was determined using the standard "3 + 3" dose escalation with planned doses ranging from 40 to 100 mg/m². IV FOLFOX was administered on the same day (oxaliplatin 100 mg/m² (day 1), leucovorin 100 mg/m² (day 1), fluorouracil 2,400 mg/m² over 46 hours (day 1)). Both IP and IV regimens were repeated every 2 weeks.

RESULTS Among the 13 patients, there was no DLT at 40 and 60 mg/m². Two patients had grade 3 febrile neutropenia at 80 mg/m², and the recommended phase II dose was 60 mg/m². Other patients underwent IP paclitaxel and FOLFOX without serious adverse events. Seven patients underwent second-look diagnostic laparoscopy, and the average change in PCI score was -7.0 ± 9.7. Conversion surgery rate was 23.1% (n = 3). The median overall survival was 16.6 months (95% confidence interval, 16.6-N/A), and progression-free survival was 9.6 months (95% confidence interval, 4.7-N/A). All adverse events were tolerable and manageable.

CONCLUSIONS The biweekly regimen of IP paclitaxel and FOLFOX is safe and the recommended dose of IP paclitaxel for a phase II trial is 60 mg/m².