Outcome of Canine Multicentric Lymphoma after Single or Divided Treatment with Cyclophosphamide in Multidrug Chemotherapy

Lee, J.; Liao, Albert; Wang, Shang-Lin

doi:10.1016/j.tcam.2020.100461

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Previous studies have found the addition of L‐asparaginase to CHOP‐based protocols does not impact response rate, duration of first remission, or survival time 16 . Additionally, cyclophosphamide administration was divided over 4 days which may affect efficacy; however, a recent study found method of cyclophosphamide administration (single vs divided) did not impact response, PFS, nor survival time 34 . Three dogs were started on prednisone prior to initiation of the RBCHOP protocol, which may have contributed to development of chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Response‐based modification of CHOP chemotherapy for canine B‐cell lymphoma

Benjamin

Sørenmo

Krick³

et al. 2021

Vet Comparative Oncology

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Despite high initial response rates, a subset of dogs with B‐cell lymphoma responds less robustly to CHOP‐based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B‐cell lymphoma were treated with a response‐based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.

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Section: Discussionmentioning

confidence: 99%

Response‐based modification of CHOP chemotherapy for canine B‐cell lymphoma

Benjamin

Sørenmo

Krick³

et al. 2021

Vet Comparative Oncology

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“…O tratamento quimioterápico do presente caso consistiu no protocolo de Wisconsin-Madison que é uma adaptação do protocolo CHOP (Chun, 2019), uma combinação de vincristina, prednisolona, ciclofosfamida e doxorrubicina, que é geralmente o tratamento usado para os casos de linfoma canino (Lee, Liao, & Wang, 2020). A duração total do tratamento consiste em 19 semanas de tratamento (Chun, 2019), sendo uma variação mais curta do período de tempo do protocolo CHOP que varia de 15 a 25 semanas.…”

Section: Resultsunclassified

Remissão total de linfoma multicêntrico em cão com o protocolo Madison-Wisconsin: Relato de caso

Lima

Silva

Araújo

et al. 2021

RSD

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O linfoma é um distúrbio do sistema hematopoiético cuja etiologia envolve a proliferação desordenada de células linfóides, no qual o linfoma multicêntrico é caracterizado pelo aumento generalizado dos linfonodos. O protocolo Madison-Wisconsin é uma das poliquimioterapias mais utilizadas no tratamento de linfomas multicêntrico em cães, sendo constituída pelos fármacos ciclofosfamida, doxorrubicina, vincristina e prednisona, e administrados de forma alternada ao longo de 19 semanas. O presente trabalho teve como objetivo relatar a eficiência do protocolo terapêutico Madison-Wisconsin na remissão total de um linfoma multicêntrico em um cão. O animal atendido foi um cão da raça Bulldog Francês, que apresentava aumento dos linfonodos submandibulares, pré-escapulares, axilares, inguinais e poplíteos e, ao exame físico, o aumento em região mesogástrica sugeriu esplenomegalia. O exame citológico dos linfonodos submandibular e poplíteo foi compatível com linfoma. No exame ultrassonográfico detectou-se aumento acentuado do baço e fígado, caracterizando o quadro de hepatoesplenomegalia. No ecodopplercardiograma foi possível observar um aumento no átrio esquerdo. Houve acompanhamento hematológico do paciente durante tratamento quimioterápico e ao longo do curso terapêutico o animal apresentou alterações no hemograma, como trombocitose e neutropenia, o que requereu um tratamento adicional. No exame bioquímico, houve aumento da ALT. Após o término da quimioterapia o animal apresentou remissão total da neoplasia demonstrando o sucesso terapêutico do protocolo de Madison-Wisconsin sobre o linfoma.

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“…Management of SHC can be difficult with a lack of effective treatments and most approaches are merely supportive in nature. As such, a number of prevention strategies have been employed including co‐administration of diuretics such as furosemide, 14,16 administration of mesna 17,18 to bind acrolein, and more recently dose fractionation 19,20 . Fractionation over 2 to 4 days may be considered to both reduce the incidence of SHC 19 .…”

Section: Introductionmentioning

confidence: 99%

“…As such, a number of prevention strategies have been employed including co-administration of diuretics such as furosemide, 14,16 administration of mesna 17,18 to bind acrolein, and more recently dose fractionation. 19,20 Fractionation over 2 to 4 days may be considered to both reduce the incidence of SHC. 19 When administered in a fractionated manner, capsule and patient size are the key determining factors.…”

Section: Introductionmentioning

confidence: 99%

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high‐grade multicentric lymphoma

Veluvolu

Willcox

Skorupski

et al. 2022

Vet Comparative Oncology

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Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days.CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200-250 mg/m 2 over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h À1 ; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h Â ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200-250 mg/m 2 .

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Outcome of Canine Multicentric Lymphoma after Single or Divided Treatment with Cyclophosphamide in Multidrug Chemotherapy

Cited by 5 publications

References 16 publications

Response‐based modification of CHOP chemotherapy for canine B‐cell lymphoma

Response‐based modification of CHOP chemotherapy for canine B‐cell lymphoma

Remissão total de linfoma multicêntrico em cão com o protocolo Madison-Wisconsin: Relato de caso

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high‐grade multicentric lymphoma

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