Peer-reviewed veterinary case report
GST gene types linked to cyclophosphamide side effects in dogs
By Ekena, J. et al.·Published in Veterinary and Comparative Oncology·2018·Department of Medical Sciences School of Veterinary Medicine, University of Wisconsin‐Madison Madison Wisconsin·View original on Crossref →
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Original publication title: Glutathione‐S‐transferase‐theta genotypes and the risk of cyclophosphamide toxicity in dogs
- Species:
- dog
Plain-English summary
A group of dogs receiving chemotherapy with cyclophosphamide (CP) were monitored for side effects like bladder inflammation and gastrointestinal issues. Researchers found that dogs with bladder problems had received higher doses of CP and were more likely to have been treated with a specific dosing method called metronomic chemotherapy. However, the genetic variations in certain detoxifying enzymes did not seem to predict which dogs would experience these toxic effects. The study aims to improve understanding of how to identify dogs at risk for these side effects in the future.
People also search for: dog chemotherapy side effects · cyclophosphamide toxicity in dogs · bladder inflammation in dogs after chemo
Abstract
The antineoplastic agent cyclophosphamide (CP) has dose‐limiting side effects including sterile haemorrhagic cystitis (SHC), bone marrow (BM) suppression and gastrointestinal (GI) toxicity in dogs. The metabolites acrolein and phosphoramide that mediate these toxicities are glutathione‐S‐transferase (GST) substrates, and low functioning GST alleles are associated with CP toxicity in humans. The aim of this study was to determine whether variants in 2 canine GST genes,GSTT1andGSTT5, were over‐represented in dogs that developed CP toxicity. Dogs undergoing pulse or metronomic CP chemotherapy were recruited (n = 101) and genotyped for 6GSTT1polymorphisms and 1GSTT56‐bp deletion that leads to non‐functional enzyme. Median cumulative CP dosages for dogs with SHC (1350 mg/m2) were significantly higher than for dogs with GI/BM toxicity (871 mg/m2) or no toxicity (991 mg/m2;P = .0012). Dogs with SHC were more likely to have had metronomic (84.2%, 16 of 19 SHC cases) vs pulse (15.8%, 3 of 19 SHC cases) CP dosing (P < .0001). All dogs with BM or GI toxicity (n = 30) had pulse chemotherapy.GSTT1andGSTT5variant allele frequencies were not significantly different in CP‐treated dogs with SHC or GI/BM toxicity compared to dogs without documented adverse effects. Work is underway to identify which canine GSTs detoxify acrolein and phosphoramide, so that better tools are available to predict the risk of CP toxicity in dogs.
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Search related cases →Original publication on Crossref: https://doi.org/10.1111/vco.12411