ABSTRACT
Canine transmissible venereal tumor (TVTC) is a highly casuistic transmissible neoplasm in Brazil. Chemotherapy with vincristine sulfate is considered the treatment of choice, but the need for weekly applications and hematological monitoring, in addition to costs, are obstacles to owners' adhesion to the treatment. Lomustine is an alkylating class antineoplastic agent, and because it is administered orally, it is a more practical and less costly treatment option for the owners of animals with neoplasms sensitive to the drug. This study evaluated the therapeutic efficacy of lomustine in dogs affected by TVTC. Twelve dogs with cytopathological diagnosis of natural genital TVTC were selected. The dogs were submitted to the experimental protocol with lomustine administration at doses of 70 to 85 mg/m2 orally every 21 days, totaling a maximum of two administration cycles. The animals were reevaluated every 7 days until a maximum of +49 days after the first dose of lomustine, to monitor the regression of neoplastic lesions through measurements. Among the 12 dogs submitted to the lomustine protocol, 8/12 achieved complete remission of the neoplasm and were considered cured (66.6%), 1/12 had partial response to treatment (8.33%) and 3/12 had stable disease (25%). Important adverse effects such as severe neutrophilic leukopenia were detected in 3/12 dogs (25%). The clinical study indicated that lomustine may be a treatment option for TVTC.
O tumor venéreo transmissível canino (TVTC) é uma neoplasia transmissível de elevada casuística no Brasil. A quimioterapia com sulfato de vincristina é considerada o tratamento de escolha, mas a necessidade de aplicações semanais e acompanhamento hematológico, além dos custos, são obstáculos à adesão dos proprietários ao tratamento. A lomustina é um antineoplásico da classe dos agentes alquilantes e, por ser administrado por via oral, representa um opção de tratamento mais prática e menos onerosa para os proprietários de animais com neoplasias. O objetivo deste estudo foi avaliar a eficácia terapêutica da lomustina em cães acometidos por TVTC. Foram selecionados 12 cães com diagnóstico citopatológico de TVTC genital de ocorrência natural. Os cães foram submetidos ao protocolo experimental com administração de lomustina nas doses de 70 a 85 mg/m2 por via oral a cada 21 dias, totalizando no máximo dois ciclos de administração. Os animais foram reavaliados a cada sete dias até um máximo de +49 dias após a primeira dose de lomustina, para monitorar a regressão das lesões neoplásicas por meio de mensuração das lesões. Entre os 12 cães submetidos ao protocolo, 8/12 obtiveram remissão completa da neoplasia e foram considerados curados (66,6%), 1/12 tiveram resposta parcial ao tratamento (8,33%) e 3/12 tiveram doença estável (25%). Efeitos adversos importantes, como leucopenia neutrofílica grave, foram detectados em 3/12 cães (25%). O estudo clínico indicou que a lomustina pode ser uma opção de tratamento para TVTC.
Subject(s)
Animals , Dogs , Venereal Tumors, Veterinary/therapy , Dog Diseases , Lomustine/therapeutic use , Neoplasms/veterinaryABSTRACT
Drug-induced liver injury (DILI) is a rare entity associated with high morbidity and mortality. It includes a broad spectrum of clinical patterns, from acute hepatitis to cirrhosis. Among the common associated drugs are antimicrobial like anti-TBC, antineoplastic, CNS agents and non-steroidal anti-inflammatory drugs. Establishing causality between DILI and a certain drug is a challenge. Some scoring systems have been evaluated, considering RUCAM score as the gold standard. We present the case of a 35-year-old woman with a history of a high-grade glioma treated with surgery and chemotherapy with lomustine, procarbazine and vincristine. She evolved with altered liver tests, predominantly cholestatic pattern, but asymptomatic. Etiologic study negative and abdominal imaging were normal. The liver biopsy was compatible with 40% ductopenia, without inflammatory elements. We consider DILI associated with the use of lomustine, with RUCAM score suggesting. After discontinuing chemotherapy and using ursodeoxycholic acid for the treatment of cholestasis there was an improvement in liver tests. There is limited evidence in the literature regarding hepatotoxicity associated with lomustine, mainly in experimental animal models. Cases of cholestatic hepatotoxicity have been described with the use of other similar nitrosureas. In relation to procarbazine and vincristine, DILI is reported mainly reversible and predominantly with hepatocellular pattern, not consistent with our case. We find it interesting to communicate with review of the literature about it.
El daño hepático inducido por drogas (DILI) es una entidad poco frecuente, con alta morbimortalidad asociada. Incluye un amplio espectro de patrones clínicos, desde hepatitis aguda a cirrosis. Dentro de los fármacos frecuentemente asociados se encuentran antibióticos como anti-TBC, agentes antineoplásicos, de acción en el SNC y anti-inflamatorios no esteroidales. Establecer una causalidad entre DILI y una determinada droga constituye un desafío. Para ello, se han evaluado diversos sistemas de puntuación, considerándose gold estándar el RUCAM score. Se presenta el caso de una mujer de 35 años de edad con antecedentes de glioma de alto grado operado y en quimioterapia con lomustina, procarbazina y vincristina. En su evolución presenta alteración de pruebas hepáticas de predominio colestásico de manera asintomática, con estudio etiológico causal negativo e imagenológico normal. La biopsia hepática fue compatible con ductopenia de 40% sin elementos inflamatorios. Se plantea DILI asociado al uso de lomustina con un score de RUCAM sugerente, decidiéndose interrumpir sus ciclos de quimioterapia e inicia tratamiento con ácido ursodesoxicólico, presentando mejoría progresiva de pruebas hepáticas. Existe evidencia limitada en la literatura en relación a hepatotoxicidad asociada a este fármaco, principalmente en modelos experimentales, y con el uso de otras nitrosureas similares se han descrito casos de hepatotoxicidad de predominio colestásico. En relación con procarbazina y vincristina existen reportes de DILI principalmente reversible y con patrón de predominio hepatocelular, lo que no es concordante con nuestro caso, por lo cual nos parece de interés comunicarlo con revisión de la literatura al respecto.
Subject(s)
Humans , Female , Adult , Cholestasis/chemically induced , Antineoplastic Agents, Alkylating/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Lomustine/adverse effects , Cholestasis/diagnosis , Chemical and Drug Induced Liver Injury/diagnosisABSTRACT
ABSTRACT Lymphoma is the most common lymphoproliferative disorder in cats. Cutaneous lymphoma, however, is a rare form of extranodal lymphoma. Recently, several cutaneous lymphomas at the tarsal region have been reported in cats. As it differs clinically and histopathologically from the common cutaneous lymphoma, it was denominated cutaneous tarsal lymphoma. The present study describes the case of a 13-year-old male domestic longhair cat that presented with a subcutaneous mass, of 30-days evolution, at the tarsal region of the right pelvic limb. Histopathology analysis showed malignant neoplasia of round cells, morphologically suggestive of large cell lymphoma. Immunohistochemistry confirmed the diagnosis of B-immunoblastic lymphoma. Patient was treated with lomustine, and prednisolone with an overall survival time of 2.1 months. The aggressiveness of this feline lymphoma reinforces the need for further studies to understand better the disease progression and to establish improved therapeutic protocols that can increase survival time and improve quality of life of these patients.
RESUMEN El linfoma representa la enfermedad linfoproliferativa más frecuente en gatos. Sin embargo, el linfoma cutáneo es una rara forma de linfoma extranodal. Recientemente, el linfoma cutáneo se reportó localizado en el tarso. Tanto clínica como histopatológicamente, esta forma difiere de la forma cutánea típica, y se denominó linfoma tarsal felino. Este estudio describe el caso de un gato, doméstico de pelo largo, 13 años de edad con una masa subcutánea, de 30 días de evolución en la región tarsal del miembro pélvico derecho. La histopatologia reveló neoplasia de células redondas, sugestiva de linfoma de células grandes. La inmunohistoquímica confirmó el diagnóstico de linfoma imunoblástico de células B. El tratamiento realizado fue lomustina y prednisolona con tiempo de sobrevida de 2,1 meses. La agresividad de este linfoma, refuerza la necesidad de estudios para entender su curso y mejorar protocolos terapéuticos que incrementen tanto la sobrevida como la calidad de vida para estos pacientes.
ABSTRACT
Metronomic chemotherapy consists of an anticancer modality treatment. It is applicable in patients at an advanced stage, with the objective of increasing overall survival. The aim of this study was to report an anal sac apocrine carcinoma case in a dog with lymph node metastasis treated with metronomic chemotherapy sequential to surgery and conventional chemotherapy using gemcitabine and carboplatin. Metronomic chemotherapy was associated with cyclooxygenase-2 (COX-2) inhibitors, due to strong tumor COX-2 immunohistochemistry expression. Metronomic chemotherapy was initiated with cyclophosphamide, but it was replaced by lomustine, also in metronomic dosage, due to adverse effects. Treatment showed effectiveness, since the patient's overall survival exceeded 1095 days (36 months), considerably higher than the mean overall survival expected for this pathology.(AU)
Quimioterapia metronômica consiste em uma modalidade de tratamento anticancerígeno, aplicável a pacientes em estadiamento avançado, com o objetivo de aumentar a sobrevida global. O objetivo deste trabalho foi relatar um caso de carcinoma apócrino do saco anal, em uma cadela, com metástase em linfonodo tratado com quimioterapia metronômica sequencial à cirurgia e quimioterapia convencional utilizando-se gencitabina e carboplatina. O tratamento metronômico foi associado ao uso de inibidores de ciclo-oxigenase-2 (COX-2), baseando-se na constatação de sua expressão tumoral. A terapia metronômica iniciou-se com ciclofosfamida, mas houve necessidade de substituição pela lomustina, também em dose metronômica, devido à ocorrência de efeitos adversos. O tratamento mostrou ser eficaz, pois a sobrevida do paciente ultrapassa 1095 dias (36 meses) desde a cirurgia, sendo consideravelmente maior que a média relatada para essa patologia.(AU)
Subject(s)
Animals , Female , Dogs , Dogs , Angiogenesis Inhibitors , Cyclophosphamide/therapeutic use , Lomustine/therapeutic use , Apocrine Glands/ultrastructure , Carcinoma/drug therapy , Carcinoma/veterinary , Lymphatic MetastasisABSTRACT
Metronomic chemotherapy consists of an anticancer modality treatment. It is applicable in patients at an advanced stage, with the objective of increasing overall survival. The aim of this study was to report an anal sac apocrine carcinoma case in a dog with lymph node metastasis treated with metronomic chemotherapy sequential to surgery and conventional chemotherapy using gemcitabine and carboplatin. Metronomic chemotherapy was associated with cyclooxygenase-2 (COX-2) inhibitors, due to strong tumor COX-2 immunohistochemistry expression. Metronomic chemotherapy was initiated with cyclophosphamide, but it was replaced by lomustine, also in metronomic dosage, due to adverse effects. Treatment showed effectiveness, since the patient's overall survival exceeded 1095 days (36 months), considerably higher than the mean overall survival expected for this pathology.(AU)
Quimioterapia metronômica consiste em uma modalidade de tratamento anticancerígeno, aplicável a pacientes em estadiamento avançado, com o objetivo de aumentar a sobrevida global. O objetivo deste trabalho foi relatar um caso de carcinoma apócrino do saco anal, em uma cadela, com metástase em linfonodo tratado com quimioterapia metronômica sequencial à cirurgia e quimioterapia convencional utilizando-se gencitabina e carboplatina. O tratamento metronômico foi associado ao uso de inibidores de ciclo-oxigenase-2 (COX-2), baseando-se na constatação de sua expressão tumoral. A terapia metronômica iniciou-se com ciclofosfamida, mas houve necessidade de substituição pela lomustina, também em dose metronômica, devido à ocorrência de efeitos adversos. O tratamento mostrou ser eficaz, pois a sobrevida do paciente ultrapassa 1095 dias (36 meses) desde a cirurgia, sendo consideravelmente maior que a média relatada para essa patologia.(AU)
Subject(s)
Animals , Female , Dogs , Angiogenesis Inhibitors , Apocrine Glands/ultrastructure , Carcinoma/drug therapy , Carcinoma/veterinary , Cyclophosphamide/therapeutic use , Lomustine/therapeutic use , Lymphatic MetastasisABSTRACT
A lomustina é um agente quimioterápico que vem sendo utilizado no tratamento do mastocitomacanino. Este trabalho tem o objetivo de avaliar os efeitos mielotóxicos induzidos por essa droga duranteo tratamento. Foram avaliados seis cães com mastocitoma utilizando lomustina. Três cães foramtratados de forma adjuvante a cirurgia, sendo dois de grau II e um de grau III e três cães de formapaliativa de grau III. Foram realizados exames clínicos gerais, hemograma completo, dosagem séricade alalino aminotransferase (ALT), fosfatase alcalina, ureia e creatinina. Dois cães apresentaram mielossupressão,com leucopenia e neutrofi lia, na primeira semana após a quimioterapia, retornando aosvalores normais na terceira semana, sem apresentar febre. Foi iniciado antibioticoterapia em ambosos animais e a dosagem posterior de lomustina foi reduzida em 30%. Os demais exames não apresentaramalterações. Os efeitos colaterais do tratamento do mastocitoma com lomustina se mostraramaceitáveis, havendo a necessidade de acompanhamento hematológico e bioquímico desses animais(AU)
The lomustine is a chemotherapic agent that has been used in the treatment of canine mast cell tumor.The odd of this paper is evaluate the myelosuppression caused by lomustine in the treatment of Mastcell Tumor (MCT) in dogs. Three dogs were treated with surgery and adjuvante chemotherapy, beingtwo grade II and one grade III and three dogs with grade III were treated with palliative chemotherapy.It was realized haemogram and plasm dosage of alanine aminotransferase, alkaline phosphatase,creatinine and urea. Two dogs presented myelossuppression with leukopenia and neutropenia in thefi rst week after the chemotherapy, returning to the normal value in the third week, without fever. Theboth dogs were treated with antibiotic therapy and the posterior dosage of lomustine was reduced in30%. The others exams didnt presented any alteration. The adverse effect of the treatment of MCTwith lomustine showed acceptable and the patients have to be monitoring with haematological and biochemistry of these animals(AU)
Subject(s)
Animals , Dogs , Lomustine/adverse effects , Lomustine/toxicity , Lomustine/therapeutic use , Mastocytoma/drug therapy , Mastocytoma/veterinary , DogsABSTRACT
A lomustina é um agente quimioterápico que vem sendo utilizado no tratamento do mastocitomacanino. Este trabalho tem o objetivo de avaliar os efeitos mielotóxicos induzidos por essa droga duranteo tratamento. Foram avaliados seis cães com mastocitoma utilizando lomustina. Três cães foramtratados de forma adjuvante a cirurgia, sendo dois de grau II e um de grau III e três cães de formapaliativa de grau III. Foram realizados exames clínicos gerais, hemograma completo, dosagem séricade alalino aminotransferase (ALT), fosfatase alcalina, ureia e creatinina. Dois cães apresentaram mielossupressão,com leucopenia e neutrofi lia, na primeira semana após a quimioterapia, retornando aosvalores normais na terceira semana, sem apresentar febre. Foi iniciado antibioticoterapia em ambosos animais e a dosagem posterior de lomustina foi reduzida em 30%. Os demais exames não apresentaramalterações. Os efeitos colaterais do tratamento do mastocitoma com lomustina se mostraramaceitáveis, havendo a necessidade de acompanhamento hematológico e bioquímico desses animais
The lomustine is a chemotherapic agent that has been used in the treatment of canine mast cell tumor.The odd of this paper is evaluate the myelosuppression caused by lomustine in the treatment of Mastcell Tumor (MCT) in dogs. Three dogs were treated with surgery and adjuvante chemotherapy, beingtwo grade II and one grade III and three dogs with grade III were treated with palliative chemotherapy.It was realized haemogram and plasm dosage of alanine aminotransferase, alkaline phosphatase,creatinine and urea. Two dogs presented myelossuppression with leukopenia and neutropenia in thefi rst week after the chemotherapy, returning to the normal value in the third week, without fever. Theboth dogs were treated with antibiotic therapy and the posterior dosage of lomustine was reduced in30%. The others exams didnt presented any alteration. The adverse effect of the treatment of MCTwith lomustine showed acceptable and the patients have to be monitoring with haematological and biochemistry of these animals