Is the blood of a surgeon performing HIPEC contaminated by irinotecan, its major metabolites and platinum compounds?

Guillaume Saint-Lorant,Simon Rodier,Agnès Palix,Jean-Marc Guilloit,Sophie Ndaw,Mathieu Melczer,Stéphanie Lagadu,Raphaël Delépée

doi:10.1515/pp-2020-0141

Abstract

ObjectivesHyperthermic intraperitoneal chemotherapy (HIPEC) is a beneficial surgical technique for patients, but the surgeons are being exposed to cytotoxic drugs. Few biomonitoring studies were led on blood samples in the context of HIPEC. This study aimed to evaluate the surgeon’s plasmatic and red blood cell (RBC) contamination by irinotecan, two of its major metabolites and platinum compounds.MethodsHIPEC procedures performed using the coliseum techniques were observed between September 2015 and April 2018 in a French comprehensive cancer center. Irinotecan and its metabolites SN-38 and APC were dosed by UHPLC with a limit of quantification determined at 50 pg/mL. Platinum compounds were dosed by inductively coupled plasma mass spectrometry with a limit of quantification determined at 16 pg/mL.ResultsDespite collective and personal protective equipment, 80% of plasma samples were contaminated by irinotecan and 33% by platinum compounds out of 21. The results showed that the surgeon was contaminated after HIPEC and even after a period of HIPEC inactivity. Nineteen percent of plasmatic samples and 45% of RBC samples were contaminated by SN-38, the active metabolite of irinotecan. APC was only found in some RBC samples (33%).ConclusionsEven if this study shows blood contamination by irinotecan, two of its major metabolites (including active SN-38) and platinum compounds both in the plasma and RBC of a surgeon performing the HIPEC procedures, further studies should be performed to confirm these results. Additional studies should be carried out to further investigate the contamination in the context of HIPEC and more broadly in the hospital.

Highlights

Hyperthermic intraperitoneal chemotherapy (HIPEC) began to be performed in the United States during 1980s and in Japan and France [1,2,3]
Even if this study shows blood contamination by irinotecan, two of its major metabolites and platinum compounds both in the plasma and red blood cell (RBC) of a surgeon performing the HIPEC procedures, further studies should be performed to confirm these results
All blood samples were collected with a constant interval between the end of the HIPEC procedure and sampling (18.5 ± 1.78 h) respecting the pharmacokinetic characteristics of irinotecan and its metabolites and the platinum compounds

Summary

Introduction

Hyperthermic intraperitoneal chemotherapy (HIPEC) began to be performed in the United States during 1980s and in Japan and France [1,2,3] The focus of this technique is metastasis carcinomatosis which is caused by macroscopic primary malignancies such as mesothelioma, pseudomyxoma and peritoneal secondary tumors, mainly from colorectal cancer. HIPEC is still being evaluated for use with the secondary origin of gastric or ovarian tumors [4, 5] This surgery can be performed using either closedabdomen or open-abdomen HIPEC techniques. The latter is called the “coliseum technique” as described by Sugarbaker [6]. Irinotecan appears to be metabolized to an active metabolite, SN-38 (300–1,000-fold more active than the parent), via carboxylesterase and to inactive metabolites, APC

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