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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2017

01-06-2017 | Gastrointestinal Oncology

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols

Authors: Markus W. Löffler, MD, Heiko Schuster, PhD, Anne Zeck, PhD, Nicolas Quilitz, BSc, Jürgen Weinreich, PhD, Alexander Tolios, MD, Sebastian P. Haen, MD, Philipp Horvath, MD, Stefan Löb, MD, Hans-Georg Rammensee, PhD, Ingmar Königsrainer, MD, Alfred Königsrainer, MD, Stefan Beckert, MD

Published in: Annals of Surgical Oncology | Issue 6/2017

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Abstract

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies with application of cytostatic drugs such as oxaliplatin (OX) after cytoreductive surgery. Despite its increased use, evidence for optimal drug dosage, and notably duration of HIPEC, is scarce.

Methods

In this study, OX distribution was comprehensively assessed in nine patients during HIPEC (300 mg OX/m2 body surface area in Physioneal solution for 30 min). Oxaliplatin and its derivatives were measured in peritoneal perfusates over time by liquid chromatography coupled with mass spectrometry (LC-MS), and the resulting total platinum concentration in tissue was analyzed by atomic absorption spectrometry. Additionally, a novel impedance-based real-time cytotoxicity assay was used to evaluate the bioactivity of perfusates ex vivo.

Results

Compared with amounts of OX expected in peritoneal perfusates by calculation, only 10–15% of the parent drug could be detected by LC-MS during HIPEC. Notably, the study additionally detected platinum compounds consistent with OX transformation, accounting for a further fraction of the applied drug. The cytotoxic properties of perfusates remained unchanged during HIPEC, with only a slight but significant attenuation evidenced after 30 min.

Conclusions

The bioactivity of peritoneal perfusates ex vivo is a useful parameter for evaluating the actual cytotoxic potential of OX and its derivatives used in HIPEC over time, overcoming important limitations and disadvantages associated with respective drug monitoring only. Ex vivo cytotoxicity assays may be a promising tool to aid guiding future standardization and harmonization of HIPEC protocols based on drug-mediated effects.
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Metadata
Title
Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols
Authors
Markus W. Löffler, MD
Heiko Schuster, PhD
Anne Zeck, PhD
Nicolas Quilitz, BSc
Jürgen Weinreich, PhD
Alexander Tolios, MD
Sebastian P. Haen, MD
Philipp Horvath, MD
Stefan Löb, MD
Hans-Georg Rammensee, PhD
Ingmar Königsrainer, MD
Alfred Königsrainer, MD
Stefan Beckert, MD
Publication date
01-06-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 6/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-5790-x

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