Risk factors for development of sterile haemorrhagic cystitis in canine lymphoma patients receiving oral cyclophosphamide: a case–control study

Gaeta, Roberto; Brown, Dorothy Cimino; Cohen, Richard L.; Sørenmo, Karin U.

doi:10.1111/vco.12009

Cited by 20 publications

(22 citation statements)

References 13 publications

(35 reference statements)

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“…It is possible that risk factors could not be identified due to the low number of dogs with SHC (n=6). Higher single doses as well as higher cumulative doses of cyclophosphamide and a prolonged application of cyclophosphamide have been described in dogs by other authors (Crow and others 1977, Hirschberger and others 2000, Charney and others 2003, Frimberger and others 2006, Gaeta and others 2012), as risk factors. Gaeta and others (2012) also reported a higher incidence of SHC in dogs of lower age, but the younger dogs received higher doses of cyclophosphamide which could also have contributed to the development of SHC.…”

Section: Discussionmentioning

confidence: 73%

Mesna and furosemide for prevention of cyclophosphamide‐induced sterile haemorrhagic cystitis in dogs – a retrospective study

2014

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Sterile haemorrhagic cystitis (SHC) is a possible side effect of cyclophosphamide which can severely impact quality of life. Mesna and diuresis are effective in human medicine to prevent SHC. The aim of the present study was to compare the efficacy of mesna versus diuresis with furosemide in preventing SHC in dogs treated with cyclophosphamide within a multidrug chemotherapy induction protocol for malignant lymphoma. Medical records of dogs treated at the Clinic of Small Animal Medicine, Munich, between 1997 and 2009 were analysed retrospectively. Of the 131 dogs included, 33 received no prophylaxis (group 1), 43 received mesna (group 2), and 55 received furosemide (group 3). Age, gender, breed, bodyweight, body surface area, dose and application method of cyclophosphamide, and the method of SHC prophylaxis were compared between dogs with and without SHC. Six dogs (4.6 per cent) developed SHC. The incidence of SHC in groups 1, 2 and 3 was 4/33 (12.1 per cent), 1/43 (2.3 per cent), and 1/55 (1.8 per cent), respectively. Dogs receiving either mesna or furosemide were significantly less likely to develop SHC (P=0.03). Otherwise no significant differences were found. In conclusion, this study demonstrates the efficacy and the medical indication of mesna and furosemide for prevention of cyclophosphamide-induced SHC.

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Section: Discussionmentioning

confidence: 73%

Mesna and furosemide for prevention of cyclophosphamide‐induced sterile haemorrhagic cystitis in dogs – a retrospective study

2014

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“…This has also been shown in dogs receiving MTD cyclophosphamide for lymphoma (Gaeta et al . ). It is unclear why the incidence of SHC was higher in this study compared with those previously reported but it may be due to our more vigilant monitoring for haematuria than in other studies.…”

Section: Discussionmentioning

confidence: 97%

Toxicity of metronomic cyclophosphamide chemotherapy in a UK population of cancer‐bearing dogs: a retrospective study

Harper

Blackwood

2017

J of Small Animal Practice

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“…The overall incidence of SHC in the University of Wisconsin‐Madison dogs enrolled in this study was 8.9%. This is comparable to other studies, in which SHC was found in 3.8% to 9.0% of pulse‐treated dogs, and in 3.6% to 32% of metronomic CP‐treated dogs Metronomic CP was a significant risk factor for SHC in our study. Cumulative CP doses were nearly 3‐fold higher with metronomic compared to pulse protocols, and higher cumulative doses are a risk factor for SHC .…”

Section: Discussionmentioning

confidence: 92%

“…This is comparable to other studies, in which SHC was found in 3.8% to 9.0% of pulse‐treated dogs, and in 3.6% to 32% of metronomic CP‐treated dogs Metronomic CP was a significant risk factor for SHC in our study. Cumulative CP doses were nearly 3‐fold higher with metronomic compared to pulse protocols, and higher cumulative doses are a risk factor for SHC . The metronomic CP protocol in our population did not include furosemide, which may have increased SHC risk .…”

Section: Discussionmentioning

confidence: 93%

Glutathione‐S‐transferase‐theta genotypes and the risk of cyclophosphamide toxicity in dogs

Ekena

Wood

Manchester

et al. 2018

Vet Comparative Oncology

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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, GSTT1 and GSTT5, were over-represented in dogs that developed CP toxicity. Dogs undergoing pulse or metronomic CP chemotherapy were recruited (n = 101) and genotyped for 6 GSTT1 polymorphisms and 1 GSTT5 6-bp deletion that leads to non-functional enzyme. Median cumulative CP dosages for dogs with SHC (1350 mg/m ) were significantly higher than for dogs with GI/BM toxicity (871 mg/m ) or no toxicity (991 mg/m ; 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. GSTT1 and GSTT5 variant 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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Risk factors for development of sterile haemorrhagic cystitis in canine lymphoma patients receiving oral cyclophosphamide: a case–control study

Cited by 20 publications

References 13 publications

Mesna and furosemide for prevention of cyclophosphamide‐induced sterile haemorrhagic cystitis in dogs – a retrospective study

Mesna and furosemide for prevention of cyclophosphamide‐induced sterile haemorrhagic cystitis in dogs – a retrospective study

Toxicity of metronomic cyclophosphamide chemotherapy in a UK population of cancer‐bearing dogs: a retrospective study

Glutathione‐S‐transferase‐theta genotypes and the risk of cyclophosphamide toxicity in dogs

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