Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients
- 388 Downloads
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.
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.
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).
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.
KeywordsMorbidity Mortality Peritoneal carcinomatosis Intraperitoneal chemotherapy Hyperthermia Cytoreductive surgery Oxaliplatin Irinotecan
We acknowledge Lorna Saint Ange for editing.
- 1.Sugarbaker PH, Cuniffe W, Belliveau JF, de Bruin E, Graves T. Rationale for perioperative intraperitoneal chemotherapy as a surgical adjuvant for gastrointestinal malignancy. Reg Cancer Treat 1988;1:66–79Google Scholar
- 5.Los G, Mutsaers PH, van der Vijgh WJ, Baldew GS, de Graaf PW, McVie JG. Direct diffusion of cisplatinum in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy. Cancer Res 1989;48:3380–4Google Scholar
- 6.Zoetmulder FA. Cancer cell seeding during abdominal surgery: experimental studies. In: Sugarbaker PH, ed. Peritoneal Carcinomatosis: Principles of Management. Boston: Kluwer Acadademic Publishers, 1996:155–62Google Scholar
- 7.Jacquet P, Elias D, Sugarbaker P. L’implantation tumorale dans les sites de cicatrisation après chirurgie des cancers digestifs. J Chir (Paris) 1996;133:175–82Google Scholar
- 13.Giachetti S, Perpoint B, Zidani R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomoduled fluorouracil-leucovorin as first line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–47Google Scholar
- 17.Elias D, Antoun A, Goharin A, et al. Research on the best chemohyperthermia technique for treatment of peritoneal carcinomatosis after complete resection. Int J Surg Invest 2000;1:431–9Google Scholar
- 23.Elias D, Dube P, Bonvalot S, et al. A treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate postoperative intraperitoneal chemotherapy. Feasibility and preliminary results. Hepatogastroenterology 1999;46:360–3PubMedGoogle Scholar