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Pharmacokinetics of Oxaliplatin During Open Versus Laparoscopically Assisted Heated Intraoperative Intraperitoneal Chemotherapy (HIPEC): An Experimental Study

  • Gynecologic Oncology
  • Original Papers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The technical feasibility of the laparoscopic approach for HIPEC has been demonstrated in a previous study. An experimental study on the porcine model was carried out to compare oxaliplatin pharmacokinetics during a laparoscopic-assisted procedure versus the coliseum technique for HIPEC.

Methods

Adult pigs received an HIPEC procedure that was based on 460 mg/m2 of oxaliplatin over 30 minutes with a perfusate heated at 41°C to 43°C. The HIPEC drains were placed in the upper and lower quadrants of the abdomen. Peritoneal fluid and blood samples were collected every 10 minutes during the procedure, and the pharmacokinetics of oxaliplatin was studied.

Results

Two groups of 10 adult pigs were studied. All the procedures were successfully completed with an adequate intra-abdominal temperature and distribution. No major technical problems were encountered. At the end of the HIPEC, 41.5% of the molecule was absorbed in the laparoscopic group compared with 33.4% in the laparotomy group (P = .0543). Peritoneal oxaliplatin half-life (T½) was significantly faster in the laparoscopic procedure (median, 37.5 vs. 59.3 minutes, P = .02). The area under the curve ratio of peritoneal to plasma reflects a more important oxaliplatin crossing through the peritoneal barrier in the laparoscopic procedure (ratio, 16.4 in the closed procedure vs. 28.1 in the open one; P = .03).

Conclusions

This study confirms the technical feasibility and reliability of the laparoscopic approach for HIPEC, and it extends knowledge concerning peritoneal drug absorption. Oxaliplatin absorption is far higher with laparoscopy in terms of time course in peritoneal perfusion. Clinical application in selected patients may be expected after further experimental investigation designed to define the adequate drug dosage.

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Acknowledgments

Supported by the research program of the Institut Claudius Regaud Cancer Center; by Sanofi-Aventis, which provided the drug; and Karl Storz Inc., which provided the laparoscopic equipment. All the experiments were carried out in the surgery laboratory of Rangueil University Hospital, Toulouse, France.

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Authors and Affiliations

  1. Department of Surgical Oncology, Institut Claudius Regaud, 20-24 Rue du Pont Pierre, 31052, Toulouse, Cedex, France

    Amélie Gesson-Paute MD, Gwenael Ferron MD & Denis Querleu MD

  2. EA3035, Institut Claudius Regaud, 20-24 Rue du Pont Pierre, 31052, Toulouse, Cedex, France

    Fabienne Thomas MD, Emanuelle Cohen de Lara MD & Etienne Chatelut MD, PhD

  3. Paul Sabatier University, University of Toulouse, Toulouse, France

    Gwenael Ferron MD, Fabienne Thomas MD, Emanuelle Cohen de Lara MD, Etienne Chatelut MD, PhD & Denis Querleu MD

Authors
  1. Amélie Gesson-Paute MD
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  2. Gwenael Ferron MD
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  3. Fabienne Thomas MD
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  4. Emanuelle Cohen de Lara MD
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  5. Etienne Chatelut MD, PhD
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  6. Denis Querleu MD
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Correspondence to Gwenael Ferron MD.

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Gesson-Paute, A., Ferron, G., Thomas, F. et al. Pharmacokinetics of Oxaliplatin During Open Versus Laparoscopically Assisted Heated Intraoperative Intraperitoneal Chemotherapy (HIPEC): An Experimental Study. Ann Surg Oncol 15, 339–344 (2008). https://doi.org/10.1245/s10434-007-9571-9

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  • DOI: https://doi.org/10.1245/s10434-007-9571-9

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