• Eur J Surg Oncol · Oct 2020

    Identification of pharmacogenetic biomarkers for efficacy of cytoreductive surgery plus hyperthermic intraperitoneal mitomycin C in patients with colorectal peritoneal metastases.

    • E C Hulshof, R J Lurvink, N Caserta, de HinghI H J TIHJTDepartment of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands., T van Wezel, S Böhringer, J J Swen, H Gelderblom, H J Guchelaar, and M J Deenen.
    • Department of Clinical Pharmacy, Catharina Hospital, Michelangelolaan 2, 5623 EJ, Eindhoven, the Netherlands; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands.
    • Eur J Surg Oncol. 2020 Oct 1; 46 (10 Pt A): 1925-1931.

    IntroductionMitomycin C (MMC) is commonly used in patients with colorectal peritoneal metastases (CPM) treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). MMC requires metabolic activation prior to exert its cytotoxic effect of which the main activating enzymes are NQO1 and POR. However, not all patients are able to activate MMC for example due to polymorphisms in the genes encoding these enzymes. The aim of this study was to investigate the association of NQO1∗2, NQO1∗3, and POR∗28 with the efficacy of CRS + HIPEC with MMC in patients with CPM.MethodA retrospective follow-up design was used to study genetic association in patients with histologically proven CPM treated with CRS + HIPEC with MMC with respect to peritoneal recurrence rate after 3 months (primary endpoint), after 6 months, disease-free survival and overall survival. Genetic polymorphisms NQO1∗2, NQO1∗3, and POR∗28 were tested for association.ResultsA total of 253 patients were included. In NQO1∗3 carriers the peritoneal recurrence rate 3 and 6 months after HIPEC was significantly higher than in wild type patients, respectively 30.0% vs 3.8% (p = 0.009) and 40.0% vs 12.1% (p = 0.031). In line with these results, NQO1∗3 was associated with a shorter disease-free survival (HR 2.04, 95% CI [1.03-4.03]). There was no significant association with overall survival (HR 1.42, 95% CI [0.66-3.07]).ConclusionCarriership of the NQO1∗3 allele is associated with worse peritoneal recurrence rate and disease-free survival. These results suggest that individualization of patients treated with CRS + HIPEC based upon pharmacogenetics may be beneficial.Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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