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Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

¹ Department of Surgical Oncology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, Cedex, France
² Intensive Care Unit, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, Cedex, France
³ Department of Anesthesiology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, Cedex, France

Correspondence: Address correspondence and reprint requests to: D. Elias, MD, Phd; E-mail: elias{at}igr.fr

Background: Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C.

Methods: A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m²) combined with irinotecan (360 mg/m²) in 2 L/m² of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m²) and leucovorin (20 mg/m²) intravenously, resulting in tritherapy.

Results: Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001).

Conclusions: This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.

Key Words: Morbidity • Mortality • Peritoneal carcinomatosis • Intraperitoneal chemotherapy • Hyperthermia • Cytoreductive surgery • Oxaliplatin • Irinotecan

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