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Closed Abdomen Hyperthermic Intraperitoneal Chemotherapy with Irinotecan and Mitomycin C: a Phase I Study

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC.

Methods

Patients with PC fulfilling the inclusion criteria were studied. All underwent cytoreductive surgery and closed abdomen HIPEC with 0.7 mg/kg MMC and an escalating dose of irinotecan. Grade 4 (National Cancer Institute grading system) surgical and hematological complications were used to identify dose-limiting toxicity (DLT).

Results

12 patients were studied. At the first dose level of irinotecan (100 mg/m2), one patient developed a grade 4 hematological toxicity. Three other patients were included at the same level with no toxicity. Three patients were then included at the second dose level (150 mg/m2 irinotecan), of whom one developed a grade 4 surgical complication. Three further patients were thus included at the second dose level. Of these three, two patients developed DLT [grade 4 neutropenia in one, grade 4 neutropenia and thrombocytopenia with an intra-abdominal lymphatic fistula requiring reoperation (grade 4 surgical complication) in the other]. Dose escalation was stopped at this level. The maximum tolerated dose of irinotecan was determined to be 100 mg/m2.

Conclusion

Closed HIPEC combining MMC and irinotecan is safe and feasible. For HIPEC, the maximum tolerated dose of irinotecan is 100 mg/m2 when used with 0.7 mg/kg MMC.

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Acknowledgment

The authors acknowledge the league against cancer of Département de l’Ain for financial support, and Pfizer for institutional support.

Conflict of interest

The authors certify that they have no commercial associations that might pose a conflict of interest in connection with this work.

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Authors and Affiliations

  1. Department of Digestive Surgery, Centre Hospitalo-Universitaire Lyon Sud, Hospices Civils de Lyon, Pierre Bénite cedex, France

    Eddy Cotte MD, Guillaume Passot MD, Naoual Bakrin MD, François-Noël Gilly MD, PhD, Aline Steghens MD & Olivier Glehen MD, PhD

  2. EA 3738, Faculté de Médecine Lyon Sud, Université Claude Bernard Lyon1, Oullins cedex, France

    Eddy Cotte MD, Guillaume Passot MD, Michel Tod PharmD, PhD, Naoual Bakrin MD, François-Noël Gilly MD, PhD & Olivier Glehen MD, PhD

  3. Department of Pharmacy, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon cedex 04, France

    Michel Tod PharmD, PhD

  4. Colorectal Research Unit, Basingstoke and North Hampshire Foundation Trust, Basingstoke, UK

    Faheez Mohamed MD, FRCSEd

Authors
  1. Eddy Cotte MD
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  2. Guillaume Passot MD
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  3. Michel Tod PharmD, PhD
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  4. Naoual Bakrin MD
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  5. François-Noël Gilly MD, PhD
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  6. Aline Steghens MD
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  7. Faheez Mohamed MD, FRCSEd
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  8. Olivier Glehen MD, PhD
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Corresponding author

Correspondence to Eddy Cotte MD.

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Cotte, E., Passot, G., Tod, M. et al. Closed Abdomen Hyperthermic Intraperitoneal Chemotherapy with Irinotecan and Mitomycin C: a Phase I Study. Ann Surg Oncol 18, 2599–2603 (2011). https://doi.org/10.1245/s10434-011-1651-1

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  • DOI: https://doi.org/10.1245/s10434-011-1651-1

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