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Avaliação da resposta biológica tumoral ao fosfato de toceranib (Palladia®) no tratamento de carcinomas
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Resumo(s)
A evolução da terapêutica oncológica tem vindo a ser acompanhada pela procura de tratamentos mais eficazes, cada vez mais direcionados, com menos efeitos adversos e que garantam ao máximo a qualidade de vida dos pacientes. O fosfato de toceranib (Palladia®) é um inibidor dos recetores das tirosina-quinases (IRTQ) indicado para o tratamento de mastocitomas cutâneos recorrentes não extirpáveis, de grau II (intermédio) ou de grau III (elevado) de Patnaik, mas que dado o seu carácter inovador na terapêutica em medicina veterinária, tem sido utilizado extra-indicações/off-label no tratamento de variados tipos de tumores caninos, geralmente após uma falha de resposta em tratamentos primários ou padrão, previamente instituídos. Este estudo teve como objetivo avaliar a resposta biológica tumoral ao fosfato de toceranib (Palladia®), utilizado em tratamentos efetuados a canídeos/pacientes oncológicos com diagnósticos de carcinomas vários, que foram seguidos clinicamente no Hospital Escolar Veterinário da Faculdade de Medicina Veterinária da Universidade de Lisboa (HEV-FMV) entre Julho de 2017 e Maio de 2022. Os resultados obtidos na avaliação da resposta biológica tumoral ao composto, com uma dose média de 2,54 ± 0,347 mg/kg, incluem 2 casos de resposta parcial (RP- 2/23; 8,69%), 14 casos de doença estável (DE- 14/23; 60,86%) e 7 casos de doença progressiva (DP- 7/23; 30,43%). Dos 14 animais com doença estável, 8 apresentaram uma evolução da condição para doença progressiva (8/14; 57,14%) durante o seguimento clínico. Nenhum dos animais em estudo apresentou resposta completa ao tratamento. Considerando um benefício clínico, na implementação do tratamento, para qualquer resultado que se considerasse resposta completa, resposta parcial ou doença estável, estimou-se um benefício clínico de 69,56% (n=16; 16/23) e uma dose média de benefício clínico de 2,51 ± 0,314 mg/kg. Para efeitos da avaliação da função de sobrevivência e progressão de doença da amostra na sua totalidade, a mediana de tempo de sobrevivência estimada foi de 501 dias e de 191 dias a mediana de tempo para progressão de doença. Em conclusão, parece-nos possível sugerir existência de benefício clínico na utilização de Palladia® extra-indicação/off-label em casos de carcinomas vários em cães com uma dose inferior à recomendada
ABSTRACT - EVALUATION OF TUMOR BIOLOGICAL RESPONSE TO TOCERANIB PHOSPHATE (PALLADIA®) IN THE TREATMENT OF CARCINOMAS - The evolution of oncologic therapy has been driven by the pursuit of more effective, increasingly targeted treatments with fewer adverse effects, aiming to maximize the quality of life for patients. Toceranib phosphate (Palladia®) is an inhibitor of tyrosine kinase receptors (RTKI) indicated for the treatment of non-resectable, grade II (intermediate) or grade III (high) recurrent cutaneous mast cell tumors, as defined by Patnaik. However, due to its innovative nature in veterinary medicine, it has been used off-label in the treatment of various types of canine tumors, typically after a lack of response to primary or standard treatments previously instituted. This study aimed to evaluate the tumor biological response to toceranib phosphate (Palladia®) used in treatments for canines/oncology patients diagnosed with various carcinomas. These patients were clinically monitored at the Veterinary School Hospital of the Faculty of Veterinary Medicine of the University of Lisbon (HEV-FMV) between July 2017 and May 2022. The results obtained in the assessment of the tumor's biological response to the compound, with an average dose of 2.54 ± 0.347 mg/kg, included 2 cases of partial response (PR - 2/23; 8.69%), 14 cases of stable disease (SD - 14/23; 60.86%), and 7 cases of progressive disease (PD - 7/23; 30.43%). Of the 14 animals with stable disease, 8 showed a progression of the condition to progressive disease (8/14; 57.14%) during clinical follow-up. None of the animals in the study achieved a complete response to treatment. Considering clinical benefit, for any outcome classified as complete response, partial response, or stable disease, a clinical benefit of 69.56% (n=16; 16/23) was estimated, with an average clinical benefit dose of 2.51 ± 0.314 mg/kg. For the assessment of overall sample survival function and disease progression, the estimated median survival time was 501 days, and the median time to disease progression was 191 days. In conclusion, it appears possible to suggest clinical benefit in the use of Palladia® off label in cases of various carcinomas in dogs at a dose lower than recommended
ABSTRACT - EVALUATION OF TUMOR BIOLOGICAL RESPONSE TO TOCERANIB PHOSPHATE (PALLADIA®) IN THE TREATMENT OF CARCINOMAS - The evolution of oncologic therapy has been driven by the pursuit of more effective, increasingly targeted treatments with fewer adverse effects, aiming to maximize the quality of life for patients. Toceranib phosphate (Palladia®) is an inhibitor of tyrosine kinase receptors (RTKI) indicated for the treatment of non-resectable, grade II (intermediate) or grade III (high) recurrent cutaneous mast cell tumors, as defined by Patnaik. However, due to its innovative nature in veterinary medicine, it has been used off-label in the treatment of various types of canine tumors, typically after a lack of response to primary or standard treatments previously instituted. This study aimed to evaluate the tumor biological response to toceranib phosphate (Palladia®) used in treatments for canines/oncology patients diagnosed with various carcinomas. These patients were clinically monitored at the Veterinary School Hospital of the Faculty of Veterinary Medicine of the University of Lisbon (HEV-FMV) between July 2017 and May 2022. The results obtained in the assessment of the tumor's biological response to the compound, with an average dose of 2.54 ± 0.347 mg/kg, included 2 cases of partial response (PR - 2/23; 8.69%), 14 cases of stable disease (SD - 14/23; 60.86%), and 7 cases of progressive disease (PD - 7/23; 30.43%). Of the 14 animals with stable disease, 8 showed a progression of the condition to progressive disease (8/14; 57.14%) during clinical follow-up. None of the animals in the study achieved a complete response to treatment. Considering clinical benefit, for any outcome classified as complete response, partial response, or stable disease, a clinical benefit of 69.56% (n=16; 16/23) was estimated, with an average clinical benefit dose of 2.51 ± 0.314 mg/kg. For the assessment of overall sample survival function and disease progression, the estimated median survival time was 501 days, and the median time to disease progression was 191 days. In conclusion, it appears possible to suggest clinical benefit in the use of Palladia® off label in cases of various carcinomas in dogs at a dose lower than recommended
Descrição
Dissertação de Mestrado Integrado em Medicina Veterinária, área científica de Clínica
Palavras-chave
Inibidor dos recetores das tirosina-quinases Fosfato de toceranib Oncologia Sobrevivência Resposta biológica tumoral Tyrosine kinase receptor inhibitor Toceranib phosphate Oncology Survival Tumor biological response
Contexto Educativo
Citação
Nunes MJA. 2024. Avaliação da resposta biológica tumoral ao fosfato de toceranib (Palladia®) no tratamento de carcinomas [dissertação de mestrado]. Lisboa: FMV-Universidade de Lisboa
Editora
Universidade de Lisboa, Faculdade de Medicina Veterinária