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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2011

01-09-2011 | Gastrointestinal Oncology

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

Authors: Eddy Cotte, MD, Guillaume Passot, MD, Michel Tod, PharmD, PhD, Naoual Bakrin, MD, François-Noël Gilly, MD, PhD, Aline Steghens, MD, Faheez Mohamed, MD, FRCSEd, Olivier Glehen, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2011

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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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Metadata
Title
Closed Abdomen Hyperthermic Intraperitoneal Chemotherapy with Irinotecan and Mitomycin C: a Phase I Study
Authors
Eddy Cotte, MD
Guillaume Passot, MD
Michel Tod, PharmD, PhD
Naoual Bakrin, MD
François-Noël Gilly, MD, PhD
Aline Steghens, MD
Faheez Mohamed, MD, FRCSEd
Olivier Glehen, MD, PhD
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1651-1

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