© 2004 European Society for Medical Oncology
Original Article |
Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance
Departments of 1 Surgical Oncology, 2 Clinical Biology, 3 Intensive Care Unit, 4 Biomedical Engineering, 5 Anesthesiology, 6 Pharmacy and 7 Medical Oncology, Institut Gustave Roussy Comprehensive Cancer Center, Villejuif, France
* Correspondence to: Dr Lucas Sideriss, Département de Chirurgie Oncologique, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif Cedex, France. Tel: +33-1-42-11-42-11; Fax: +33-1-42-11-52-56; Email: aetos73{at}hotmail.com
Background: The purpose of this study was to report the pharmacokinetics (PK) and tolerance profile of intraoperative intraperitoneal chemo-hyperthermia (IPCH) with oxaliplatin and irinotecan.
Patients and methods: Thirty-nine patients with peritoneal carcinomatosis (PC) of either gastrointestinal or peritoneal origin underwent complete cytoreductive surgery followed by IPCH with a stable dose of oxaliplatin (460 mg/m2), plus one among seven escalating doses of irinotecan (from 300 to 700 mg/m2). IPCH was carried out with the abdomen open, for 30 min at 43°C, with 2 l/m2 of a 5% dextrose instillation in a closed continuous circuit. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before IPCH to maximize the effect of oxaliplatin and irinotecan.
Results: Irinotecan concentration in tumoral tissue increased until 400 mg/m2 and then remained stable despite dose escalations. It was 16–23 times higher than in non-bathed tissues. Increasing doses of intraperitoneal irinotecan did not modify the PK of intraperitoneal oxaliplatin, and the drug concentration ratio was 17.8 higher in tumoral tissue (bathed) than in non-bathed tissues. The hospital mortality rate was 2.5% and the non-hematological complication rate was 25%. However, grade 3–4 hematological toxicity rate was 58%.
Conclusion: Intraperitoneal heated oxaliplatin (460 mg/m2) plus irinotecan (400 mg/m2) presented an advantageous PK profile and was tolerated by patients, despite a high hematological toxicity rate.
Key words: cytoreductive surgery, hyperthermia, intraperitoneal chemotherapy, irinotecan, oxaliplatin, peritoneal carcinomatosis