Incidence of sterile hemorrhagic cystitis in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide: 55 cases (2009–2015)

Chan, Catherine M.; Frimberger, Angela E.; Moore, Antony S.

doi:10.2460/javma.249.12.1408

Cited by 19 publications

(25 citation statements)

References 26 publications

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“…Furosemide may reduce the incidence of cystitis when given concurrently (Charney et al, 2003;Best and Fry, 2013) and thus was suggested in this case. A small study also suggested similar benefit in low-dose or metronomic cyclophosphamide scheduling which is more akin to the treatment given in the current case (Chan et al, 2016).…”

Section: Introductionmentioning

confidence: 55%

Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neutropenia and an absence of lymphocytosis

Elliott¹,

Villiers

2018

Open Vet J.

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In humans, large granular lymphocytic leukaemia (LGLL) is a low-grade, indolent lymphoproliferative disorder of large granular lymphocytes (LGL) associated with autoimmune disorders; including rheumatoid arthritis and single or multiple cytopenias; particularly neutropenia. Therapy largely centres around immunosuppression which aims to resolve the immune-mediated secondary pathology, often without eradicating the neoplastic clone. The most effective agents appear to be cyclophosphamide, cyclosporine and methotrexate. This case report describes the presentation, diagnostics, therapeutic approach and outcome of a 6 year-old Golden Retriever presenting with severe neutropenia. Chlorambucil, prednisolone and cyclosporine failed to improve the neutropenia but subsequent cyclophosphamide resulted in a sustained albeit temporary improvement in neutrophil count and the ability to withdraw prophylactic antibacterials. This case closely mirrors the diagnostics and therapeutic response in human LGLL.

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Section: Introductionmentioning

confidence: 55%

Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neutropenia and an absence of lymphocytosis

Elliott¹,

Villiers

2018

Open Vet J.

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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%

“…For each dog, the following data were recorded: signalment, tumour type, CP dosing and frequency, route of administration, cumulative CP dose, and clinical outcomes of SHC, myelosuppression or GI toxicity. Concurrent drug administration was recorded, including NSAIDs and furosemide or prednisone …”

Section: Methodsmentioning

confidence: 99%

“…Concurrent drug administration was recorded, including NSAIDs 13 and furosemide or prednisone. [14][15][16][17] The presence of SHC was defined as newly observed haematuria with pollakiuria or stranguria and a negative urine culture, at any time during CP treatment. 18 BM and GI toxicities were determined from the history, physical examination and CBC during the 7 to 10 days after intermittent CP administration.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Sterile hemorrhagic cystitis (SHC), commonly reported with the use of cyclophosphamide, was not observed in this study. Chan et al (2016) used furosemide concurrently with cyclophosphamide during MC and suggested that furosemide protects against cyclophosphamide-induced SHC.…”

Section: Discussionmentioning

confidence: 99%

Microvessel density assessment in canine mammary carcinomas as a predictive factor for metronomic chemotherapy

Ferrari

Carreira³

et al. 2019

SCA

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The canine mammary tumor is the neoplasia that most commonly affects intact female dogs (not spayed) in routine veterinary practice. Canine mammary tumor therapy is a challenge because only few effective treatments have been described for high-grade tumors in veterinary medicine. One such therapeutic option that slows down tumor growth is metronomic chemotherapy (MC), a therapeutic modality that acts by decreasing tumor angiogenesis. Quantification of intratumoral microvessel density (MVD) has been proposed as a means to evaluate the effectiveness of MC in human and canine tumors. In this study, MVD is proposed as a predictive factor for the effectiveness of MC in canine mammary tumors. Twenty female dogs with mammary carcinoma were equally distributed into a mastectomy group treated only with mastectomy, and a MC group treated with MC (cyclophosphamide and piroxicam) orally and daily for 28 days followed by mastectomy. Mammary tumors were classified and graded histologically. MVD was ascertained by CD31 immunostaining. The analysis showed statistically significant difference in MVD scores between groups, corroborating a quantitative reduction in tumor microvasculature in the group treated with MC. Our findings suggest that MVD may be an important predictive factor for the selection of female dogs with malignant mammary tumors that may benefit from MC.

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Incidence of sterile hemorrhagic cystitis in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide: 55 cases (2009–2015)

Cited by 19 publications

References 26 publications

Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neutropenia and an absence of lymphocytosis

Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neutropenia and an absence of lymphocytosis

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

Microvessel density assessment in canine mammary carcinomas as a predictive factor for metronomic chemotherapy

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