Avaliação da terapia com talidomida em neoplasias malignas da glândula mamária canina
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Data
2016-09-02
Autores
Campos, Cecília Bonolo de [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
As neoplasias da glândula mamária canina são as neoplasias mais comuns em cadelas não castradas, sendo pelo menos 50% malignas. A maioria dos carcinomas invasores é relacionado a uma sobrevida inferior a dois anos quando tratados apenas com cirurgia, sendo a principal forma de tratamento da doença. A talidomida tem demonstrado benefício clínico em diversas doenças neoplásicas e não-neoplásicas, principalmente devido aos seus efeitos antiangiogênicos e imunomodulatórios. Assim, o objetivo do presente trabalho foi avaliar os efeitos terapêuticos da talidomida em cadelas diagnosticadas com neoplasias malignas da glândula mamária. Inicialmente, os eventos adversos do tratamento com talidomida foram avaliados em 29 cadelas tratadas com 20 e 10 mg/kg/dia, durante 6 meses. O fármaco foi bem tolerado, não interferindo na qualidade de vida dos animais. Em casos de sonolência excessiva a dose de 10 mg/kg deve ser preconizada. Em seguida, 58 cadelas foram divididas entre quatro diferentes tratamentos propostos: tratamento cirúrgico; cirurgia seguido de quimioterapia em dose máxima tolerada (QDMT); cirurgia, QDMT e talidomida; e cirurgia, QDMT e quimioterapia metronômica (QM). Não houve diferença estatística significativa na sobrevida global (SG) entre os quatro tratamentos propostos quando animais de todos os estadiamento clínicos foram avaliados (p=0,3177). Porém, quando avaliamos a sobrevida de animais diagnosticados com metástase à distância, os tratamentos com cirurgia, QDMT e talidomida ou QM apresentaram maiores SG (463 e 376,5 dias, respectivamente) quando comparados aos tratamentos consistindo em cirurgia e cirurgia e QDMT (150 e 148 dias, respectivamente). Além disso, relatamos o caso de uma cadela diagnosticada com um carcinossarcoma que, após diagnóstico de metástase pulmonar, sobreviveu 20 meses sendo submetida apenas ao tratamento com talidomida. O tratamento com cirurgia, QDMT e talidomida foi considerado eficaz e seguro em pacientes com estadiamento avançado, aumentando a SG de pacientes com metástase à distância. A QM pode ser associada ao tratamento cirúrgico e quimioterápico quando a talidomida não estiver disponível.
The neoplasms of the canine mammary gland are the most common neoplasm in intact female dogs, and at least 50% are malignant. Most invasive carcinomas present a survival lower than two years when treated solely with surgery, which consists in the main treatment approach for the disease. Thalidomide has demonstrated clinical benefit in several neoplastic and non-neoplastic diseases, mainly due to its antiangiogenic and immunomodulatory properties. Therefore, the aim of the present study was to evaluate the therapeutic effects of thalidomide in female dogs diagnosed with malignant neoplasms of the mammary gland. Initially, the adverse events of the thalidomide treatment were evaluated in 29 female dogs treated with 20 and 10 mg/kg/day during 6 months. The drug was well tolerated, not interfering with the activities of daily living of most of the studied population. In cases where excessive somnolence was present the 10 mg/kg/day should be indicated. Afterwards, 58 female dogs were divided into four different treatment proposals: surgical treatment, surgery followed by maximum tolerated dose chemotherapy (MTDC), surgery, MTDC, and thalidomide, and surgery, MTDC, and metronomic chemotherapy (MC). No statistically significant difference in overall survival (OS) was observed between the four proposed treatments when animals presenting all clinical stages were evaluated (p=0.3177). However, the analysis of OS of animals presenting distant metastasis, the surgery, MTDC associated to thalidomide and MC presented a longer OS, 463 and 376.5 days, respectively, when compared to the surgical and surgery plus MTDC protocols, 150 and 148 days, respectively. Furthermore, we report the case of a female dog diagnosed with a carcinosarcoma that presented a 20-month OS following the diagnosis of pulmonary metastasis solely treated with thalidomide. The treatment with surgery, MTDC and thalidomide was considered effective and safe in canine patients with advanced stage mammary gland neoplasms, increasing the OS of patients diagnosed with distant metastasis. MC may be associated to surgery and chemotherapy when thalidomide is not available.
The neoplasms of the canine mammary gland are the most common neoplasm in intact female dogs, and at least 50% are malignant. Most invasive carcinomas present a survival lower than two years when treated solely with surgery, which consists in the main treatment approach for the disease. Thalidomide has demonstrated clinical benefit in several neoplastic and non-neoplastic diseases, mainly due to its antiangiogenic and immunomodulatory properties. Therefore, the aim of the present study was to evaluate the therapeutic effects of thalidomide in female dogs diagnosed with malignant neoplasms of the mammary gland. Initially, the adverse events of the thalidomide treatment were evaluated in 29 female dogs treated with 20 and 10 mg/kg/day during 6 months. The drug was well tolerated, not interfering with the activities of daily living of most of the studied population. In cases where excessive somnolence was present the 10 mg/kg/day should be indicated. Afterwards, 58 female dogs were divided into four different treatment proposals: surgical treatment, surgery followed by maximum tolerated dose chemotherapy (MTDC), surgery, MTDC, and thalidomide, and surgery, MTDC, and metronomic chemotherapy (MC). No statistically significant difference in overall survival (OS) was observed between the four proposed treatments when animals presenting all clinical stages were evaluated (p=0.3177). However, the analysis of OS of animals presenting distant metastasis, the surgery, MTDC associated to thalidomide and MC presented a longer OS, 463 and 376.5 days, respectively, when compared to the surgical and surgery plus MTDC protocols, 150 and 148 days, respectively. Furthermore, we report the case of a female dog diagnosed with a carcinosarcoma that presented a 20-month OS following the diagnosis of pulmonary metastasis solely treated with thalidomide. The treatment with surgery, MTDC and thalidomide was considered effective and safe in canine patients with advanced stage mammary gland neoplasms, increasing the OS of patients diagnosed with distant metastasis. MC may be associated to surgery and chemotherapy when thalidomide is not available.
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Palavras-chave
Cão, Mama, Metástase, Quimioterapia Metronômica, Oncologia, Sobrevida Global, Dog, Mammary, Metastasis, Metronomic Chemotherapy, Oncology, Overall Survival