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

Harper, Aaron; Blackwood, Laura

doi:10.1111/jsap.12635

Cited by 11 publications

(17 citation statements)

References 28 publications

(39 reference statements)

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“…MC with cyclophosphamide was related to mild toxicity and SHC resolved with the use of supportive treatment. SHC was documented in a total of 31% of dogs in this study, which is similar to previous reports . However, this is likely biased by the study population and the shorter survival time.…”

Section: Discussionsupporting

confidence: 89%

“…Diuretics were not used concurrently in any of the dogs receiving MC though they might be considered to reduce the likelihood of SHC in treated dogs, as reported in a recent study . Furthermore, monitoring for haematuria was not standardized between the different institutions, which may lead to under‐reporting of SHC …”

Section: Discussionmentioning

confidence: 99%

“…SHC was documented in a total of 31% of dogs in this study, which is similar to previous reports. 22,23 However, this is likely biased by the study population and the shorter survival time. Diuretics were not used concurrently in any of the dogs receiving MC though they might be considered to reduce the likelihood of SHC in treated dogs, as reported in a recent study.…”

Section: Survival Time and Comparison Between Groupsmentioning

confidence: 99%

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Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

Treggiari

Borrego²,

Gramer³

et al. 2019

Vet Comparative Oncology

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Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first‐line adjuvant anthracycline (AC) or metronomic (MC)‐based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC‐ or MC‐based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety‐three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47‐3352) and the overall median TTP was 185 days (range 37‐1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47‐3352 days), 338 days for the AMC group (range 79‐1623 days) and 225 days for the MC group (range 57‐911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Survival Time and Comparison Between Groupsmentioning

confidence: 99%

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Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

Treggiari

Borrego²,

Gramer³

et al. 2019

Vet Comparative Oncology

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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: 99%

“…[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. Toxicities were graded from 0 to 5 based on VCOG-CTCAE v1.1 criteria.…”

Section: Introductionmentioning

confidence: 99%

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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Treating Cancer in Geriatric Pets

2017

Canine and Feline Geriatric Oncology: Honoring the Human-Animal Bond

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

Cited by 11 publications

References 28 publications

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

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

Treating Cancer in Geriatric Pets

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