Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance

• Published in: Annals of oncology Vol. 15; no. 10; pp. 1558 - 1565
• Main Authors: Elias, D., Matsuhisa, T., Sideris, L., Liberale, G., Drouard-Troalen, L., Raynard, B., Pocard, M., Puizillou, J. M., Billard, V., Bourget, P., Ducreux, M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2004
• Subjects: Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Camptothecin - pharmacokinetics; Carcinoma - drug therapy; Carcinoma - surgery; Combined Modality Therapy; cytoreductive surgery; Female; Humans; hyperthermia; Hyperthermia, Induced; Infusions, Parenteral; intraperitoneal chemotherapy; Irinotecan; Male; Medical sciences; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - pharmacokinetics; Oxaliplatin; peritoneal carcinomatosis; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - surgery; Pharmacology. Drug treatments; Tumors; Antineoplastic agent; Temperature; Resection; Carcinosis; Environmental factor; Metastasis; peritoneal carcinomatosis; Intraperitoneal; Isomerases; Oxaliplatin; Surgery; intraperitoneal chemotherapy; Platinum II Complexes; hyperthermia; Enzyme; DNA topoisomerase; cytoreductive surgery; Enzyme inhibitor; Tolerance; Malignant tumor; Irinotecan; Heat; Chemotherapy; Treatment; Distribution; Pharmacokinetics; Induced hyperthermia; Peritoneum
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdh398

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.