Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after complete cytoreductive surgery. An experimental study on the porcine model was carried out to demonstrate the feasibility of the laparoscopic approach and to compare oxaliplatin pharmacoki-netics during a laparoscopic assisted vs. the “coliseum” technique for HIPEC.
In the first step, feasibility of the peritonectomy procedure followed by HIPEC was evaluated in five adult pigs. In the second step, ten adult pigs were selected to receive laparoscopic assisted HIPEC procedure and ten pigs were selected for standard HIPEC in laparotomy. The HIPEC procedure was based on 460 mg/m2 of oxaliplatin for 30 min with a heated perfusate at 41–43 °C. HIPEC drains were placed in the upper and lower quadrants of the abdomen. Peritoneal fluid and blood samples were collected every 10 min during the procedure and the pharmacokinetics of oxaliplatin was studied.
For the first step, the procedure was successfully completed with an adequate intrabdominal temperature and distribution. For the second step, no major technical problems were encountered. At the end of the HIPEC, 41.5% of the chemotherapy was absorbed in the laparoscopic group compared to 33.4% in the laparotomy group (p = 0.0543). The peritoneal oxaliplatin half-life (T 1/2) was significantly shorter in the laparoscopic procedure (median value of 37.5 min vs. 59.3 min, p = 0.02). The area under the curve ratio for peritoneal/plasma reflects a faster oxaliplatin absorption through the peritoneal barrier in the laparoscopic procedure (ratio: 16.4 in the laparoscopic group vs. 28.1 in the laparotomy group, p = 0.03).
This study confirms the technical feasibility and reliability of the laparoscopic approach for HIPEC, and improves understanding of peritoneal drug absorption. Oxaliplatin absorption is significantly higher with laparoscopy, regarding time course in the peritoneal perfusion. Clinical application in selected patients may be expected after further experimental investigation designed to define adequate drug dosage.
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Acknowledgments
This study was supported by the research program of the Institut Claudius Regaud Cancer Centre, Comprehensive cancer center by Sanofi-Aventis who provided the drug and Karl Storz INC. who provided the laparoscopic equipment. All experiments were carried out in the surgery laboratory of the Rangueil university Hospital in Toulouse, France.
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Ferron, G., Gesson-Paute, A., Gladieff, L., Thomas, F., Chatelut, E., Querleu, D. (2009). Laparoscopically Assisted Heated Intra-Operative Intraperitoneal Chemotherapy (HIPEC): Technical Aspect and Pharmacokinetics Data. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_38
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DOI: https://doi.org/10.1007/978-1-60327-459-3_38
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