So Hyun Kang1, Sa-Hong Min2, Jin Won Kim3,4, Eunju Lee1, Sang Woo Park1, Sangjun Lee1, Hyeon Jeong Oh5,6, Young Suk Park1,7, Yoon Jin Lee8,9, Ji-Won Kim10,11, Sang-Hoon Ahn1,7, Yun-Suhk Suh1,7, Keun-Wook Lee10,11, Hye Seung Lee6,12, Hyung-Ho Kim1,7. 1. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea. 2. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. sahongmin@gmail.com. 3. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. jwkim@snubh.org. 4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. jwkim@snubh.org. 5. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea. 6. Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. 7. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. 8. Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea. 9. Department of Radiology, Seoul National University College of Medicine, Seoul, Korea. 10. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. 11. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. 12. Department of Pathology, Seoul National University Hospital, Seoul, Korea.
Abstract
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.
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.
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