Estudo dos efeitos dos fármacos anti-neoplásicos em cães com linfoma e osteossarcoma
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2010
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A utilização da quimioterapia oncológica no tratamento do linfoma canino e do osteossarcoma constitui uma opção terapêutica cada vez mais utilizada com resultados favoráveis. Contudo esta abordagem terapêutica está associada a diversos efeitos adversos em vários parâmetros fisiológicos do animal. Durante este estudo foram sujeitos a tratamento de quimioterapia oncológica 9 cães com linfoma e 3 animais com osteossarcoma. O presente estudo pretendeu avaliar os efeitos adversos provocados pelos fármacos anti-neoplásicos administrados, através da análise do hemograma, dos sinais clínicos exibidos pelos animais e informações referidas pelos proprietários. Após o diagnóstico citológico/histopatológico, o protocolo utilizado no tratamento dos animais com o linfoma foi o Madison-Wisconson short. Após a confirmação histopatológica e tratamento cirúrgico do osteossarcoma apendicular, os animais foram submetidos a quimioterapia adjuvante com a doxorrubicina e a carboplatina alternadamente, durante 6 ciclos consecutivos. Nos animais com linfoma, a forma anatómica mais comum foi o linfoma multicêntrico com 66,7% dos casos. A forma anatómica do linfoma cutâneo representou 22,2% dos casos e o linfoma intestinal 11,1% dos casos. No presente estudo, no grupo dos animais com linfoma, a doxorrubicina provocou trombocitopenia em 29,4% das suas administrações, embora sem complicações clínicas. A ciclofosfamida provocou neutropenia em 33,3% dos ciclos em que foi utilizada, contudo, a vincristina foi responsável por episódios mais graves. Após a sua administração, dois dos animais foram hospitalizados, com valores de neutrófilos de 950 células/µl e de 510 células/µl, sendo necessário reduzir a dose em posteriores administrações desse composto. Nos animais medicados com vincristina foi necessário adiar os ciclos de tratamento em 15,9% das suas utilizações, seguido da ciclofosfamida em 11,1% das suas administrações. O fármaco anti-neoplásico com o qual se observou um maior número efeitos adversos gastrintestinais foi a doxorrubicina, sendo os efeitos adversos de intensidade leve a moderada. Em 22,2% dos animais substituiu-se a ciclofosfamida pelo clorambucil após revelarem hematúria compatível com a cistite hemorrágica estéril. A doxorrubicina provocou reacções anafiláticas em 22,2% dos animais, pelo que nos subsequentes ciclos de tratamento substituiu-se este fármaco anti-neoplásico pelo mitoxantrone. No grupo dos animais com osteossarcoma ocorreram dois episódios de neutropenia ligeira após a administração da carboplatina em diferentes animais, com valores de 2270 neutrófilos/µl e 2510 neutrófilos/µl, respectivamente. Não houve necessidade de adiar os ciclos de quimioterapia nem reduzir as doses dos fármacos anti-neoplásicos. Nenhum animal necessitou de hospitalização. Os animais com osteossarcoma sujeitos a quimioterapia adjuvante demonstraram efeitos adversos gastrintestinais leves a moderados: em 66,7% das administrações da doxorrubicina registaram-se episódios de náusea/anorexia e em 44,4% dos ciclos em que a carboplatina foi utilizada provocou sintomatologia gastrintestinal leve. No grupo de animais com linfoma, apenas 4 animais permanecem vivos e 2 encontram-se ainda em tratamento. O tempo médio de sobrevida situa-se nos 153,9 dias (intervalo entre 11 e 607 dias). O grupo de animais com osteossarcoma alcançou um tempo de sobrevida total médio de 233,7 dias após o diagnóstico (com intervalo de 158 a 319 dias). Pela reduzida casuística deste estudo não foi possível correlacionar os fármacos anti-neoplásicos com alterações nos parâmetros fisiológicos nos animais. O protocolo Madison-Wisconson short utilizado no tratamento do linfoma provoca toxicidade hematológica e gastrintestinal leve a moderada, sendo necessário, em alguns animais, o adiamento dos ciclos e/ou rectificação da dose dos fármacos anti-neoplásicos administrados, podendo mesmo necessitarem de hospitalização. A carboplatina e a doxorrubicina administradas como quimioterapia adjuvante em animais com osteossarcoma, parecem ser seguras e clinicamente bem toleráveis nas doses convencionais.
The use of chemotherapy in the treatment of canine lymphoma and osteosarcoma constitutes a therapeutic option that has been increasingly used with positive results. However, this therapeutic approach is associated to several adverse effects on various physiological parameters of the animal. During this study 9 dogs with lymphoma and 3 animals with osteosarcoma were submitted to chemotherapy treatment. This study aimed to evaluate the adverse effects caused by anticancer drugs, through the analysis of hemogram, clinical signs exhibited by the animals and information provided by their owners. After the cytologic/histopathology diagnosis, the protocol used in the treatment of the animals with lymphoma was the Madison-Wisconson short. After histopathological confirmation and surgical treatment of appendicular osteosarcoma, the animals were subjected to adjuvant chemotherapy with doxorubicin and carboplatin alternately for 6 consecutive cycles. In the group of animals with lymphoma, the most common anatomical form found was the multicentric lymphoma, in 66.7% of the cases. The anatomical form of the cutaneous lymphoma accounted for 22.2%, while the intestinal lymphoma represented 11.1% of cases. In this study, in the group of the animals with lymphoma, doxorubicin caused thrombocytopenia in 29.4% of their administrations, but without clinical complications. Cyclophosphamide caused neutropenia in 33.3% of the cycles in which it was used, however, vincristine was responsible for more severe episodes. After its administration, two animals were hospitalized, with values of neutrophils of 950 cells/µl and 510cells/µl, which required a dose reduction in the subsequent administrations of this compound. In the animals treated with vincristine it was necessary to delay the treatment cycles in 15.9% of treatments, followed by cyclophosphamide in 11.1% of its administrations. The anticancer drug that had adverse gastrointestinal effects was doxorubicin, being these effects mild to moderate. In 22.2% of the animals cyclophosphamide was replaced by chlorambucil, after it revealed hematuria compatible with sterile hemorrhagic cystitis. Doxorubicin caused anaphylactic reactions in 22.2% of the animals, so in the subsequent treatment cycles it was replaced by mitoxantrone. In the group of the animals with osteosarcoma there were two episodes, in different animals, of mild neutropenia after administration of carboplatin, with values of 2270 neutrophils/µl and 2510 neutrophils/ µl, respectively. There was no need to neither delay the cycles of chemotherapy nor reduce the doses of anticancer drugs. No animal required hospitalization. Animals subjected to adjuvant chemotherapy for osteosarcoma showed mild to moderate gastrointestinal adverse effects: in 66.7% of the administrations of doxorubicin there were episodes of nausea/anorexia and in 44.4% of the cycles in which carboplatin was used, it caused gastrointestinal mild symptoms. In the group of the animals with lymphoma, only four animals survived and two are still in treatment. The median survival time stands at 153.9 days (range between 11 and 607 days). The group of the animals with osteosarcoma had a median survival time that reached a mean total of 233.7 days after diagnosis (interval 158-319 days). Due to our small sampling it was not possible to correlate the anticancer drugs with the changes in the physiological parameters of the animals. The protocol Madison-Wisconson short used in the treatment of lymphoma causes mild to moderate hematologic and gastrointestinal toxicity, which required, in some of the animals, the delay of the cycles and/or reduction of the dose of anticancer drugs administered and even hospitalization. Carboplatin and doxorubicin, administered as adjuvant chemotherapy for osteosarcoma in the animals, appear to be clinically safe and well tolerated in conventional doses.
The use of chemotherapy in the treatment of canine lymphoma and osteosarcoma constitutes a therapeutic option that has been increasingly used with positive results. However, this therapeutic approach is associated to several adverse effects on various physiological parameters of the animal. During this study 9 dogs with lymphoma and 3 animals with osteosarcoma were submitted to chemotherapy treatment. This study aimed to evaluate the adverse effects caused by anticancer drugs, through the analysis of hemogram, clinical signs exhibited by the animals and information provided by their owners. After the cytologic/histopathology diagnosis, the protocol used in the treatment of the animals with lymphoma was the Madison-Wisconson short. After histopathological confirmation and surgical treatment of appendicular osteosarcoma, the animals were subjected to adjuvant chemotherapy with doxorubicin and carboplatin alternately for 6 consecutive cycles. In the group of animals with lymphoma, the most common anatomical form found was the multicentric lymphoma, in 66.7% of the cases. The anatomical form of the cutaneous lymphoma accounted for 22.2%, while the intestinal lymphoma represented 11.1% of cases. In this study, in the group of the animals with lymphoma, doxorubicin caused thrombocytopenia in 29.4% of their administrations, but without clinical complications. Cyclophosphamide caused neutropenia in 33.3% of the cycles in which it was used, however, vincristine was responsible for more severe episodes. After its administration, two animals were hospitalized, with values of neutrophils of 950 cells/µl and 510cells/µl, which required a dose reduction in the subsequent administrations of this compound. In the animals treated with vincristine it was necessary to delay the treatment cycles in 15.9% of treatments, followed by cyclophosphamide in 11.1% of its administrations. The anticancer drug that had adverse gastrointestinal effects was doxorubicin, being these effects mild to moderate. In 22.2% of the animals cyclophosphamide was replaced by chlorambucil, after it revealed hematuria compatible with sterile hemorrhagic cystitis. Doxorubicin caused anaphylactic reactions in 22.2% of the animals, so in the subsequent treatment cycles it was replaced by mitoxantrone. In the group of the animals with osteosarcoma there were two episodes, in different animals, of mild neutropenia after administration of carboplatin, with values of 2270 neutrophils/µl and 2510 neutrophils/ µl, respectively. There was no need to neither delay the cycles of chemotherapy nor reduce the doses of anticancer drugs. No animal required hospitalization. Animals subjected to adjuvant chemotherapy for osteosarcoma showed mild to moderate gastrointestinal adverse effects: in 66.7% of the administrations of doxorubicin there were episodes of nausea/anorexia and in 44.4% of the cycles in which carboplatin was used, it caused gastrointestinal mild symptoms. In the group of the animals with lymphoma, only four animals survived and two are still in treatment. The median survival time stands at 153.9 days (range between 11 and 607 days). The group of the animals with osteosarcoma had a median survival time that reached a mean total of 233.7 days after diagnosis (interval 158-319 days). Due to our small sampling it was not possible to correlate the anticancer drugs with the changes in the physiological parameters of the animals. The protocol Madison-Wisconson short used in the treatment of lymphoma causes mild to moderate hematologic and gastrointestinal toxicity, which required, in some of the animals, the delay of the cycles and/or reduction of the dose of anticancer drugs administered and even hospitalization. Carboplatin and doxorubicin, administered as adjuvant chemotherapy for osteosarcoma in the animals, appear to be clinically safe and well tolerated in conventional doses.
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Dissertação de Mestrado em Medicina Veterinária
Palavras-chave
Linfoma canino , Tumor ósseo primário , Quimioterapia oncológica , Ciclofosfamida , Vincristina , Efeitos adversos , Toxicidade gastrintestinal , Neutropenia , Trombocitopenia