Cardiotoxicidade induzida pela doxorrubicina em cães
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2017
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A doxorrubicina é um agente antineoplásico bastante utilizado em Medicina Veterinária, integrando a escolha no tratamento de uma série de tumores sólidos e hematopoiéticos. Contudo, está descrito que o seu uso poderá estar associado ao desenvolvimento de cardiotoxicidade em cães, que pode ser classificada como aguda ou crónica, diferindo entre si pela apresentação clínica e prognóstico. Em cães, são vários os estudos que relatam o desenvolvimento de cardiomiopatia secundária ao uso do fármaco, que é em tudo semelhante a cardiomiopatia dilatada canina. A cardiotoxicidade crónica é considerada dose dependente e surge, mais comumente, quando é atingida a dose cumulativa de 240 mg/m2, contudo já foi descrita com dose de apenas 90mg/m2. O prognóstico é considerado grave, dado que a progressão poderá induzir insuficiência cardíaca congestiva refratária e/ou arritmias fatais.
Desta forma, o objetivo deste trabalho incidiu na avaliação das implicações da doxorrubicina a nível cardíaco, avaliando uma série de parâmetros no decorrer do protocolo de quimioterapia, por forma a permitir o diagnóstico precoce de cardiotoxicidade, otimizando o uso do fármaco, antes do desenvolvimento de disfunção cardíaca.
No trabalho prático foram avaliados 5 casos clínicos (1 prospetivo e 4 retrospetivos) de cães submetidos a tratamento simples ou combinado com doxorrubicina no Hospital Veterinário do Porto. A dose cumulativa máxima atingida no trabalho foi de 120mg/m2 e a mínima de 30mg/m2. Apenas 2 dos 5 cães manifestaram alterações consideradas significativas e sugestivas de cardiotoxicidade induzida pela doxorrubicina. Neste trabalho foi possível depreender que a cardiotoxicidade pode iniciar a sua manifestação em fases muito precoces do tratamento, com dose cumulativa de apenas 30 mg/m2. Curiosamente, os animais que foram submetidos a dose cumulativa menor manifestaram alterações mais significativas, quando comparados com os animais que receberam dose mais elevada. Não foi verificada maior predisposição dos animais com doença cardíaca pré-existente para desenvolvimento de cardiotoxicidade. Da mesma forma, não foi denotado desenvolvimento de alterações de condução ou ritmo, sugestivas de cardiotoxicidade aguda.
Este trabalho demonstrou que a monitorização dos cães, com recurso à associação de ecocardiografia e biomarcadores cardíacos, tornou possível a deteção precoce de alterações cardíacas, sugestivas de cardiotoxicidade induzida pela doxorrubicina.
Doxorubicin is an antineoplastic agent widely used in Veterinary Medicine for the treatment of a high number of solid and hematopoietic tumors. However, its use has been associated with the development of cardiotoxicity in dogs, which can be classified as acute or chronic. The difference between them is the clinic presentation and prognosis. In dogs, there are several studies that report the development of secondary cardiomyopathy due to this drug, which is similar to canine dilated cardiomyopathy. Chronic cardiotoxicity is considered to be dose dependent and it comes up more commonly when the cumulative dose reaches 240mg/m2; however, it has been reported with dose as low as 90mg/m2. The prognosis is poor, because the progression can induce refractory congestive heart failure and / or life threatening arrhythmias. Thus, this study focused on the evaluation of the cardiac implications of doxorubicin, through the evaluation of a number of parameters during the course of the chemotherapy, leading to the early diagnosis of cardiotoxicity, in order to optimize the use of the drug, before the development of cardiac dysfunction. In the practical work 5 cases of dogs (1 prospective and 4 retrospective), subjected to simple or combinated treatment with doxorubicin at the Hospital Veterinário do Porto, were assessed. The maximum cumulative dose reached in the study was 120 mg / m2 and the minimum was 30 mg / m2. Only 2 of the 5 dogs showed changes that were considered significant and suggestive of cardiotoxicity induced by doxorubicin. With this work it was possible to conclude that the cardiotoxicity can start its demonstration at very early stages of the treatment, with cumulative dose as low as 30 mg/m2. Interestingly, animals that underwent the lowest cumulative dose expressed the most significant changes, compared to animals that received the highest dose. There was no greater susceptibility for the animals with pre-existing heart disease to the development of cardiotoxicity. Likewise, it has not been denoted the development of conduction or rhythm cardiac changes that would suggest acute cardiotoxicity. This study showed that through the monitoring of dogs, using the combination of echocardiography and cardiac biomarkers, it was possible to achieve early detection of cardiac abnormalities, suggestive of doxorubicin induced cardiotoxicity.
Doxorubicin is an antineoplastic agent widely used in Veterinary Medicine for the treatment of a high number of solid and hematopoietic tumors. However, its use has been associated with the development of cardiotoxicity in dogs, which can be classified as acute or chronic. The difference between them is the clinic presentation and prognosis. In dogs, there are several studies that report the development of secondary cardiomyopathy due to this drug, which is similar to canine dilated cardiomyopathy. Chronic cardiotoxicity is considered to be dose dependent and it comes up more commonly when the cumulative dose reaches 240mg/m2; however, it has been reported with dose as low as 90mg/m2. The prognosis is poor, because the progression can induce refractory congestive heart failure and / or life threatening arrhythmias. Thus, this study focused on the evaluation of the cardiac implications of doxorubicin, through the evaluation of a number of parameters during the course of the chemotherapy, leading to the early diagnosis of cardiotoxicity, in order to optimize the use of the drug, before the development of cardiac dysfunction. In the practical work 5 cases of dogs (1 prospective and 4 retrospective), subjected to simple or combinated treatment with doxorubicin at the Hospital Veterinário do Porto, were assessed. The maximum cumulative dose reached in the study was 120 mg / m2 and the minimum was 30 mg / m2. Only 2 of the 5 dogs showed changes that were considered significant and suggestive of cardiotoxicity induced by doxorubicin. With this work it was possible to conclude that the cardiotoxicity can start its demonstration at very early stages of the treatment, with cumulative dose as low as 30 mg/m2. Interestingly, animals that underwent the lowest cumulative dose expressed the most significant changes, compared to animals that received the highest dose. There was no greater susceptibility for the animals with pre-existing heart disease to the development of cardiotoxicity. Likewise, it has not been denoted the development of conduction or rhythm cardiac changes that would suggest acute cardiotoxicity. This study showed that through the monitoring of dogs, using the combination of echocardiography and cardiac biomarkers, it was possible to achieve early detection of cardiac abnormalities, suggestive of doxorubicin induced cardiotoxicity.
Descrição
Dissertação de Mestrado Integrado em Medicina Veterinária
Palavras-chave
Antineoplásicos , Doxorrubicina , Cardiotoxicidade , Cães , Cardiopatias