Pharmacokinetic Study of Perioperative Intravenous Ifosfamide

Kurt Van Der Speeten,Haile Mahteme,O Anthony Stuart,Paul H Sugarbaker

doi:10.1155/2011/185092

Abstract

The use of cancer chemotherapy and hyperthermia as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5–42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy. The concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm. Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion. Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations. 4-Hydroxyifosfamide within peritoneal surface cancer nodules suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room.

Highlights

The use of intraoperative systemic chemotherapy to target peritoneal carcinomatosis in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was first explored by Elias and coworkers [1]
The peritoneal fluid levels rapidly increased; in all patients peritoneal fluid remained lower than the plasma ifosfamide levels throughout the 90-minute infusion
A clear understanding of the pharmacology of perioperative intraperitoneal hyperthermic chemotherapy combined with systemic chemotherapy in the operating room may provide important information for the design of an optimal treatment for peritoneal surface malignancy

Summary

Introduction

The use of intraoperative systemic chemotherapy to target peritoneal carcinomatosis in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was first explored by Elias and coworkers [1]. With this regimen combining intravenous 5-fluorouracil with intraperitoneal oxaliplatin, they reported a median survival of 62.7 months in a selected group of patients with carcinomatosis from colon cancer [2]. Schlemmer and coworkers in a randomized controlled study determined the response of retroperitoneal sarcoma to systemic ifosfamide with and without the addition of deep hyperthermia [3] Both the sarcoma response and the survival of patients were improved by adding hyperthermia

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Results

Discussion

Conclusion