Lomustine for treatment of canine transmissible venereal tumor / Eficácia da lomustina no tratamento do tumor venéreo transmissível canino

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.

Canine mast cell tumour lomustine's sensitization by tyrosine kinase inhibitors

Background: Tyrosine kinase inhibitors (TKIs) may sensitize neoplasms to conventional antineoplastic agents, however such studies are scarse in the veterinary literature and there is no in vivo study about this subject. Although the literature recommend consensual about the use of masitinib for unresectable or metastatic MCTs, the potential of tumour sensitization to chemotherapeutic agents exerted by the drug is poorly explored in veterinary medicine. The objective of this paper was to report, for the first time, the sensitization of 2 canine mast cell tumours (MCTs) to lomustine, with the use of 2 tyrosine kinase inhibitors: masitinib and toceranib. Cases: Two dogs were referred due tumour recurrence in the left pelvic limb (dog 1), and unilateral mass in the right nasal mucocutaneous region (dog 2). The first case was a 8-year-old female Pinscher, and the second case refers to a 8-year-old male mixed-breed dog. Fine needle aspiration of both lesions was performed, and the cytological analysis were compatible with high grade canine MCT. In the first case, it was started a chemotherapeutic treatment with intravenous vinblastine (2 mg/m² ), associated with prednisolone (40 mg/m2 , every 24 h for 7 days), followed by 25 mg/m2 every 24 h, for more 30 days, tramadol (4 mg/kg every 8 h, until new recommendations) and gabapentin (3 mg/kg every 12 h, until new recommendations). However, there was no objective response, and vinblastine was substituted by lomustine (60 mg/m2 every 21 days), however there was also no response after 2 doses. After masitinib importation, the same was started at 12.5 mg/kg orally every 24 h, but there was also no objective response. However, after new lomustine administration the lesion showed complete remission. The second dog initiated its treatment with toceranib, recently licensed in Brazil, at a dosage of 2.7 mg/kg every 48 h, and after 30 days, there was partial remission. However, the remaining lesion still deemed unresectable, and systemic chemotherapy with lomustine (50 mg/m2 ) was initiated along with continuous toceranib. After 3 weeks of the first chemotherapy complete remission was noted and a second dose was administered. Once the patient remained in complete clinical remission, only toceranib was maintained at the same dose. After 11 months using the toceranib, there was sign of disease recurrence and lomustine was re-initiated resulting in complete remission. Discussion: The TKIs masitinib and toceranib might be considered the first-line therapy for unresectable and/or metastatic canine MCT, but also for those cases with confirmed internal tandem duplications in the exon 11 of the c-KIT protooncogene. Masitinib appears to be more selective than others TKI, such as toceranib, imatinib, dasatinib and sunitinib, because it causes weak inhibition of BCR/ABL (breakpoint cluster region-Abelson), Fms (macrophage colony-stimulating factor receptor), Flt-3 (FMS-like tyrosine kinase-3) and VEGFR (vascular endothelial growth factor receptor), which may partially explains its increased safety and lower risk of cardiotoxicity. In the first case, the animal has been treated with lomustine associated to masitinib and showed a progression-free interval of 33 days, however, the response reported may have been lower, due previously exposition to chemotherapeutic agents, which might compromise the response to TKI. The second case, with the association of lomustine and toceranib, was followed up for 365 days, presenting only one recurrence in the final third of the follow-up, however, with subsequent new complete remission. Sensitization of canine MCT to lomustine with TKIs increases the therapeutic possibilities for this neoplasm, mainly in patients with advanced stage and high-grade tumours.

Tumor Venéreo Transmissível (TVT) nasal com metástase óssea em um cão / Nasal transmissible venereal tumor (TVT) with bone metastasis in a dog

Background: Transmissible venereal tumor (TVT) is a highly contagious round cell neoplasm that affects dogs, and itis usually transmitted through coitus. The tumor is mainly located in the genital area; however, the neoplasm can also beextragenital, affecting the nose, mouth, and eyes, as well as the skin and superficial lymph nodes. Cytological examinationis the most commonly used method for definitive diagnosis due to its low cost and fast execution. Chemotherapy, radiotherapy, surgical resection, and other procedures such as cryosurgery are the possible treatment options. The objective ofthis report was to describe a case of extragenital TVT with nasal primary site and metastasis in the bone tissue in a dogtreated at a private veterinary hospital in the city of Belém, Pará, Brazil.Case: A 6-year-old male domiciliary Labrador Retriever dog, weighing 24.2 kg, received oncologic treatment in a privateveterinary hospital in the city of Belém, Pará, Brazil. The animal had a history of neoplastic disease, and he had undergoneTVT resection associated with chemotherapy treatment more than 3 years ago. The clinical examination revealed a volumeincrease in the periorbital region, left lateral ocular displacement, left nostril excessive epistaxis, recurrent sneezing, cough,and pain signs, and tumor metastasis was suspected. Complementary exams of oncological cytology, computed tomography(CT), hemogram, and serum biochemistry were requested for diagnosis and staging of the condition, and supportive therapywas prescribed. The cytological report showed a dense population of neoplastic round cells with characteristics of TVT. CTindicated the presence of a heterogeneous hypodense mass with irregular contours and partially defined limits, with slightuptake of the intravenously injected contrast medium that obliterated the nasal cavity, maxillary recess, nasopharyngealmeatus, frontal sinus, and sphenoid sinus on the left side...

Tumor Venéreo Transmissível (TVT) nasal com metástase óssea em um cão / Nasal transmissible venereal tumor (TVT) with bone metastasis in a dog

Background: Transmissible venereal tumor (TVT) is a highly contagious round cell neoplasm that affects dogs, and itis usually transmitted through coitus. The tumor is mainly located in the genital area; however, the neoplasm can also beextragenital, affecting the nose, mouth, and eyes, as well as the skin and superficial lymph nodes. Cytological examinationis the most commonly used method for definitive diagnosis due to its low cost and fast execution. Chemotherapy, radiotherapy, surgical resection, and other procedures such as cryosurgery are the possible treatment options. The objective ofthis report was to describe a case of extragenital TVT with nasal primary site and metastasis in the bone tissue in a dogtreated at a private veterinary hospital in the city of Belém, Pará, Brazil.Case: A 6-year-old male domiciliary Labrador Retriever dog, weighing 24.2 kg, received oncologic treatment in a privateveterinary hospital in the city of Belém, Pará, Brazil. The animal had a history of neoplastic disease, and he had undergoneTVT resection associated with chemotherapy treatment more than 3 years ago. The clinical examination revealed a volumeincrease in the periorbital region, left lateral ocular displacement, left nostril excessive epistaxis, recurrent sneezing, cough,and pain signs, and tumor metastasis was suspected. Complementary exams of oncological cytology, computed tomography(CT), hemogram, and serum biochemistry were requested for diagnosis and staging of the condition, and supportive therapywas prescribed. The cytological report showed a dense population of neoplastic round cells with characteristics of TVT. CTindicated the presence of a heterogeneous hypodense mass with irregular contours and partially defined limits, with slightuptake of the intravenously injected contrast medium that obliterated the nasal cavity, maxillary recess, nasopharyngealmeatus, frontal sinus, and sphenoid sinus on the left side...(AU)

LOPH and D-MHC in the treatment of FeLV associated acute leukemia in a cat

Background: Bone marrow primary malignancies are denominated leukemias, classified as myeloid or lymphoid, according to the cell lineage, and acute or chronic, according to the cell´s state of maturation. In cats, acute lymphoid leukemiais the most common form, especially in regions endemic for feline leukemia virus and / or feline immunodeficiency virus.A new treatment protocol for lymphomas, called LOPH, was described for animals with FeLV persistent viremia. Thisstudy aimed to report a case of a cat presenting with FeLV associated acute leukemia and treated with the LOPH protocol,and, in the rescue phase, a modification of the D-MAC protocol, denominated D-MHC.Case: A 4-year-old mixed breed intact queen was attended due to lethargy and inappetence. The patient did not present anyrelevant abnormalities in the clinical exam and complementary exams were performed including complete blood count,biochemical profile, SNAP Feline Triple Test, chest radiographs and abdominal ultrasound. Imaging tests and biochemicalvalues were unremarkable, but the patient presented a reagent result for FeLV and severe leukocytosis due to lymphocytosis. The morphological evaluation of the blood smear revealed the presence of blasts, in a concentration greater than 20%of the nucleated cells, which allowed the characterization of a leukemic state, probably lymphoid. First-line treatmentwas based on the LOPH protocol, including Lomustine, Vincristine, Prednisolone and Doxorubicin, in four-week cycles.Nevertheless, during the third cycle, 66 days after the institution of this protocol, the patient presented a febrile conditionalong with marked leukocytosis due to lymphocytosis, confirming leukemia recurrence. A rescue attempt was performedwith a modification of the D-MAC protocol, originally consisting of the combination of dexamethasone, melphalan, actinomycin-D and cytarabine, but with replacement of actinomycin-D by doxorubicin, and therefore denominated D-MHC....

LOPH and D-MHC in the treatment of FeLV associated acute leukemia in a cat

Background: Bone marrow primary malignancies are denominated leukemias, classified as myeloid or lymphoid, according to the cell lineage, and acute or chronic, according to the cell´s state of maturation. In cats, acute lymphoid leukemiais the most common form, especially in regions endemic for feline leukemia virus and / or feline immunodeficiency virus.A new treatment protocol for lymphomas, called LOPH, was described for animals with FeLV persistent viremia. Thisstudy aimed to report a case of a cat presenting with FeLV associated acute leukemia and treated with the LOPH protocol,and, in the rescue phase, a modification of the D-MAC protocol, denominated D-MHC.Case: A 4-year-old mixed breed intact queen was attended due to lethargy and inappetence. The patient did not present anyrelevant abnormalities in the clinical exam and complementary exams were performed including complete blood count,biochemical profile, SNAP Feline Triple Test, chest radiographs and abdominal ultrasound. Imaging tests and biochemicalvalues were unremarkable, but the patient presented a reagent result for FeLV and severe leukocytosis due to lymphocytosis. The morphological evaluation of the blood smear revealed the presence of blasts, in a concentration greater than 20%of the nucleated cells, which allowed the characterization of a leukemic state, probably lymphoid. First-line treatmentwas based on the LOPH protocol, including Lomustine, Vincristine, Prednisolone and Doxorubicin, in four-week cycles.Nevertheless, during the third cycle, 66 days after the institution of this protocol, the patient presented a febrile conditionalong with marked leukocytosis due to lymphocytosis, confirming leukemia recurrence. A rescue attempt was performedwith a modification of the D-MAC protocol, originally consisting of the combination of dexamethasone, melphalan, actinomycin-D and cytarabine, but with replacement of actinomycin-D by doxorubicin, and therefore denominated D-MHC....(AU)

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk / Resultado da quimioterapia adjuvante com lomustina, vimblastina e clorambucil no manejo do mastocitoma canino de risco alto a intermediário

In spite of the many available protocols, the use of chemotherapy for the management of canine mast cell tumours (MCT) remains empirical, and there is lack of criteria for the choice of protocol and definition of patients who may benefit from treatment. The objective of this study was to evaluate the outcome of dogs with MCT after adjuvant chemotherapy according to the risk of recurrence or metastasis proposed on the literature. This prospective study included 89 followed up dogs with prognosis assesment including clinical, histological, immunohistochemical and genetic features of canine MCT. Patients were grouped according to risk of recurrence and metastasis and recommended treatment with lomustine followed by chlorambucil if considered at high-risk, or vinblastine followed by chlorambucil if a patient was at intermediate risk. Outcome was defined by disease-free interval (DFI) and overall survival (OS) estimated by Kaplan-Meier curve. Adjuvant lomustine was useful for control of canine MCT of high-risk of recurrence or metastasis, but only when sequentially associated to chlorambucil with a DFI of 686 days and not reached OS. There was no difference in outcome in the intermediate-risk group despite choosen treatment. Patients at intermediate-to-low risk may not require adjuvant treatments, even in the absence of free surgical margins.(AU)

Apesar dos inúmeros protocolos disponíveis, o uso da quimioterapia permanece empírico para o mastocitoma canino e faltam critérios para escolha do protocolo e da definição dos pacientes que poderiam se beneficiar do tratamento. O objetivo deste estudo foi avaliar o resultado de cães com mastocitoma após a quimioterapia adjuvante, de acordo com o risco de recorrência ou metástase proposto na literatura. Este estudo prospectivo incluiu 89 cães com acompanhamento clínico e avaliação prognóstica, incluindo características clínicas, histológicas, imuno-histoquímicas e genéticas dos mastocitomas. Os pacientes foram agrupados segundo o risco de recorrência ou metástase, sendo recomendado tratamento com lomustina seguida de clorambucila, se considerados sob alto risco, ou vimblastina seguida de clorambucila, se estivessem sob risco intermediário. O resultado final foi definido pelo intervalo livre de doença (ILD) e pela sobrevida global (SG), estimados pela curva de Kaplan-Meier. Na adjuvância, a lomustina foi útil no controle do mastocitoma canino de alto risco, mas apenas quando associada ao clorambucila, com um ILD de 686 dias, sem atingir a mediana para SG. Não houve diferença no grupo de risco intermediário, independentemente do tratamento escolhido. Pacientes de risco intermediário podem não necessitar de tratamentos adjuvantes, mesmo na ausência de margens cirúrgicas livres.(AU)

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk / Resultado da quimioterapia adjuvante com lomustina, vimblastina e clorambucil no manejo do mastocitoma canino de risco alto a intermediário

In spite of the many available protocols, the use of chemotherapy for the management of canine mast cell tumours (MCT) remains empirical, and there is lack of criteria for the choice of protocol and definition of patients who may benefit from treatment. The objective of this study was to evaluate the outcome of dogs with MCT after adjuvant chemotherapy according to the risk of recurrence or metastasis proposed on the literature. This prospective study included 89 followed up dogs with prognosis assesment including clinical, histological, immunohistochemical and genetic features of canine MCT. Patients were grouped according to risk of recurrence and metastasis and recommended treatment with lomustine followed by chlorambucil if considered at high-risk, or vinblastine followed by chlorambucil if a patient was at intermediate risk. Outcome was defined by disease-free interval (DFI) and overall survival (OS) estimated by Kaplan-Meier curve. Adjuvant lomustine was useful for control of canine MCT of high-risk of recurrence or metastasis, but only when sequentially associated to chlorambucil with a DFI of 686 days and not reached OS. There was no difference in outcome in the intermediate-risk group despite choosen treatment. Patients at intermediate-to-low risk may not require adjuvant treatments, even in the absence of free surgical margins.(AU)

Apesar dos inúmeros protocolos disponíveis, o uso da quimioterapia permanece empírico para o mastocitoma canino e faltam critérios para escolha do protocolo e da definição dos pacientes que poderiam se beneficiar do tratamento. O objetivo deste estudo foi avaliar o resultado de cães com mastocitoma após a quimioterapia adjuvante, de acordo com o risco de recorrência ou metástase proposto na literatura. Este estudo prospectivo incluiu 89 cães com acompanhamento clínico e avaliação prognóstica, incluindo características clínicas, histológicas, imuno-histoquímicas e genéticas dos mastocitomas. Os pacientes foram agrupados segundo o risco de recorrência ou metástase, sendo recomendado tratamento com lomustina seguida de clorambucila, se considerados sob alto risco, ou vimblastina seguida de clorambucila, se estivessem sob risco intermediário. O resultado final foi definido pelo intervalo livre de doença (ILD) e pela sobrevida global (SG), estimados pela curva de Kaplan-Meier. Na adjuvância, a lomustina foi útil no controle do mastocitoma canino de alto risco, mas apenas quando associada ao clorambucila, com um ILD de 686 dias, sem atingir a mediana para SG. Não houve diferença no grupo de risco intermediário, independentemente do tratamento escolhido. Pacientes de risco intermediário podem não necessitar de tratamentos adjuvantes, mesmo na ausência de margens cirúrgicas livres.(AU)

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk

ABSTRACT In spite of the many available protocols, the use of chemotherapy for the management of canine mast cell tumours (MCT) remains empirical, and there is lack of criteria for the choice of protocol and definition of patients who may benefit from treatment. The objective of this study was to evaluate the outcome of dogs with MCT after adjuvant chemotherapy according to the risk of recurrence or metastasis proposed on the literature. This prospective study included 89 followed up dogs with prognosis assesment including clinical, histological, immunohistochemical and genetic features of canine MCT. Patients were grouped according to risk of recurrence and metastasis and recommended treatment with lomustine followed by chlorambucil if considered at high-risk, or vinblastine followed by chlorambucil if a patient was at intermediate risk. Outcome was defined by disease-free interval (DFI) and overall survival (OS) estimated by Kaplan-Meier curve. Adjuvant lomustine was useful for control of canine MCT of high-risk of recurrence or metastasis, but only when sequentially associated to chlorambucil with a DFI of 686 days and not reached OS. There was no difference in outcome in the intermediate-risk group despite choosen treatment. Patients at intermediate-to-low risk may not require adjuvant treatments, even in the absence of free surgical margins.

RESUMO Apesar dos inúmeros protocolos disponíveis, o uso da quimioterapia permanece empírico para o mastocitoma canino e faltam critérios para escolha do protocolo e da definição dos pacientes que poderiam se beneficiar do tratamento. O objetivo deste estudo foi avaliar o resultado de cães com mastocitoma após a quimioterapia adjuvante, de acordo com o risco de recorrência ou metástase proposto na literatura. Este estudo prospectivo incluiu 89 cães com acompanhamento clínico e avaliação prognóstica, incluindo características clínicas, histológicas, imuno-histoquímicas e genéticas dos mastocitomas. Os pacientes foram agrupados segundo o risco de recorrência ou metástase, sendo recomendado tratamento com lomustina seguida de clorambucila, se considerados sob alto risco, ou vimblastina seguida de clorambucila, se estivessem sob risco intermediário. O resultado final foi definido pelo intervalo livre de doença (ILD) e pela sobrevida global (SG), estimados pela curva de Kaplan-Meier. Na adjuvância, a lomustina foi útil no controle do mastocitoma canino de alto risco, mas apenas quando associada ao clorambucila, com um ILD de 686 dias, sem atingir a mediana para SG. Não houve diferença no grupo de risco intermediário, independentemente do tratamento escolhido. Pacientes de risco intermediário podem não necessitar de tratamentos adjuvantes, mesmo na ausência de margens cirúrgicas livres.

Tratamento de um mastocitoma de alto grau na língua de um cão por meio de radioterapia e quimioterapia: relato de caso / Treatment of a canine high grade lingual mast cell tumor with radiation therapy and chemotherapy: case report

Um canino da raça Boxer, fêmea, de oito anos de idade, foi atendido com salivação, halitose e disfagia. No exame clínico, foi observada uma massa ulcerada no terço médio da língua medindo 3,5 x 4,0cm. A histopatologia e a imuno-histoquímica levaram ao diagnóstico de um mastocitoma de alto grau. O tratamento cirúrgico (glossectomia parcial) foi declinado pelo proprietário, sendo a radioterapia indicada em seu lugar. O protocolo radioterápico empregado foi 15 frações de 300cGy, realizadas cinco vezes por semana. O equipamento utilizado foi de ortovoltagem. A lesão neoplásica apresentou remissão clínica completa a partir da quarta sessão radioterápica. O único efeito colateral observado foi mucosite leve na região irradiada, que, entretanto, não levou a sintomas clínicos. A quimioterapia sistêmica consistiu de vimblastina e lomustina, alternadas a cada 14 dias, durante quatro meses. Até o momento (22 meses após o tratamento), não há evidências de recidiva local ou metástases do mastocitoma. A associação da radioterapia e da quimioterapia pode ser considerada uma alternativa terapêutica nos casos de mastocitomas irressecáveis, já que, neste caso, levou à remissão completa e duradoura de um tumor agressivo, com ótima tolerância do paciente ao tratamento e posterior qualidade de vida.(AU)

An 8 year old female boxer was presented with salivation, halitosis and dysphagia. In the clinical examination, an ulcerated mass in the middle third of the tongue was observed, measuring 3.5 x 4.0cm. Histopathology and immunohistochemistry the confirmed diagnosis of a high-grade mast cell tumor. Surgical treatment (partial glossectomy) was declined by owner, and radiotherapy was indicated. The protocol consisted of fifteen daily fractions of 300 cGy each. The equipment used was an orthovoltage unit. The tumor had complete clinical remission after the fourth session, and mild mucositis was the only side effect observed. Systemic chemotherapy was performed with vinblastine and lomustine, alternated every 14 days, during four months. There is no evidence of local recurrence or metastasis in this patient twenty-two months after treatment. The combination of radiation therapy and chemotherapy can be considered as an alternative therapy in cases of unresectable mast cell tumors. It led to complete and durable remission of an aggressive tumor, with great quality of life.(AU)

Tratamento de um mastocitoma de alto grau na língua de um cão por meio de radioterapia e quimioterapia: relato de caso / Treatment of a canine high grade lingual mast cell tumor with radiation therapy and chemotherapy: case report

Um canino da raça Boxer, fêmea, de oito anos de idade, foi atendido com salivação, halitose e disfagia. No exame clínico, foi observada uma massa ulcerada no terço médio da língua medindo 3,5 x 4,0cm. A histopatologia e a imuno-histoquímica levaram ao diagnóstico de um mastocitoma de alto grau. O tratamento cirúrgico (glossectomia parcial) foi declinado pelo proprietário, sendo a radioterapia indicada em seu lugar. O protocolo radioterápico empregado foi 15 frações de 300cGy, realizadas cinco vezes por semana. O equipamento utilizado foi de ortovoltagem. A lesão neoplásica apresentou remissão clínica completa a partir da quarta sessão radioterápica. O único efeito colateral observado foi mucosite leve na região irradiada, que, entretanto, não levou a sintomas clínicos. A quimioterapia sistêmica consistiu de vimblastina e lomustina, alternadas a cada 14 dias, durante quatro meses. Até o momento (22 meses após o tratamento), não há evidências de recidiva local ou metástases do mastocitoma. A associação da radioterapia e da quimioterapia pode ser considerada uma alternativa terapêutica nos casos de mastocitomas irressecáveis, já que, neste caso, levou à remissão completa e duradoura de um tumor agressivo, com ótima tolerância do paciente ao tratamento e posterior qualidade de vida.(AU)

An 8 year old female boxer was presented with salivation, halitosis and dysphagia. In the clinical examination, an ulcerated mass in the middle third of the tongue was observed, measuring 3.5 x 4.0cm. Histopathology and immunohistochemistry the confirmed diagnosis of a high-grade mast cell tumor. Surgical treatment (partial glossectomy) was declined by owner, and radiotherapy was indicated. The protocol consisted of fifteen daily fractions of 300 cGy each. The equipment used was an orthovoltage unit. The tumor had complete clinical remission after the fourth session, and mild mucositis was the only side effect observed. Systemic chemotherapy was performed with vinblastine and lomustine, alternated every 14 days, during four months. There is no evidence of local recurrence or metastasis in this patient twenty-two months after treatment. The combination of radiation therapy and chemotherapy can be considered as an alternative therapy in cases of unresectable mast cell tumors. It led to complete and durable remission of an aggressive tumor, with great quality of life.(AU)

Clinical and laboratorial evaluation of dogs with cutaneous lymphoma treated with lomustine / Avaliação clínica e laboratorial de cães com linfoma cutâneo tratados com lomustina

The aim of this prospective study was to evaluate the clinical response of dogs with cutaneous lymphoma treated with lomustine (CCNU) and to identify possible adverse effects and toxicity during treatment. Fifteen dogs, seven females and eight males aged between five and 17 years old, diagnosed with cutaneous lymphoma by histopathological analysis were selected and treated with lomustine at 90 mg/m² every three weeks. Monitoring was carried out and consisted of the assessment of laboratory hematology and serum chemistry before and during treatment. Partial response was observed in 53.3% of the animals. None of the animals achieved a complete response and seven dogs (46.6%) had progressive disease. The median survival time was 22 days. The major hematological and biochemical changes found after therapy were leukopenia (73.3%), thrombocytopenia (60%) and anemia (46.1%). Renal and liver toxicity was observed in 40% and 73.3% of dogs, respectively. Hematocrit, total protein, leukocyte count, neutrophil count, serum creatinine, ALT, GGT, alkaline phosphatase and urine specific gravity were affected during therapy. The use of lomustine as a monotherapy in the treatment of canine cutaneous lymphoma was effective; however, adverse effects occurred and compromised the quality of life of the majority of dogs in this study. Therefore, lower doses of lomustine should be considered in future studies(AU)

O objetivo deste estudo prospectivo foi avaliar a resposta clínica de cães com linfoma cutâneo tratados com lomustina (CCNU) e identificar possíveis efeitos adversos e toxicidade durante o tratamento. Quinze cães, sendo 7 fêmeas e 8 machos, com idades entre 5 e 17 anos diagnosticados com linfoma cutâneo por avaliação histopatológica foram selecionados e tratados com lomustina na dose de 90 mg/m2 a cada três semanas. Os cães foram monitorados por avaliação hematológica e bioquímica sérica antes e durante o tratamento. A resposta parcial foi observada em 53,3% dos animais. Nenhum dos animais apresentou resposta completa e sete animais (46,6%) apresentaram progressão da doença. O tempo médio de sobrevida foi de 22 dias. As principais alterações hematológicas e bioquímicas observadas após o tratamento foram leucopenia (73,3%), trombocitopenia (60%) e anemia (46,1%). Sinais de toxicidade renal e hepática foram observados em 40% e 73,3% dos cães, respectivamente. Durante o tratamento foram afetados os parâmetros hematócrito, proteínas séricas totais, contagem de leucócitos, contagem de neutrófilos, creatinina sérica, ALT, GGT, fosfatase alcalina e densidade urinária. O uso de lomustina como monoterapia no tratamento do linfoma cutâneo canino foi efetivo; entretanto, efeitos adversos ocorreram e comprometeram a qualidade de vida da maioria dos animais neste estudo. Assim, sugere-se que doses mais baixas de lomustina sejam consideradas em estudos futuros(AU)

Ciclooxygenase inhibitor and metronomic chemotherapy association for the treatment of metastatic anal sac carcinoma in dog: case report / Inibidor de ciclo-oxigenase associado à quimioterapia metronômica no tratamento de carcinoma de saco anal metastático canino: relato de caso

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)

Ciclooxygenase inhibitor and metronomic chemotherapy association for the treatment of metastatic anal sac carcinoma in dog: case report / Inibidor de ciclo-oxigenase associado à quimioterapia metronômica no tratamento de carcinoma de saco anal metastático canino: relato de caso

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)

CONTRIBUIÇÕES AO ESTUDO DO TUMOR VENÉREO TRANSMISSÍVEL CANINO

O tumor venéreo transmissível canino (TVTC) é uma das neoplasias mais comuns em cães, e acomete principalmente os animais com livre acesso à rua, uma vez que é transmitida predominantemente através do coito. O tratamento de eleição é através de quimioterapia com sulfato de vincristina endovenoso, com intervalos semanais e custo elevado, o que muitas vezes dificulta a continuidade do tratamento para os tutores dos animais acometidos. A lomustina é um agente quimioterápico que é administrado por via oral, com intervalo de 21 dias entre as aplicações, o que facilita a adesão ao tratamento por parte dos tutores. O estudo descrito no capítulo 1 intitulado Eficácia da lomustina no tratamento do tumor venéreo transmissível canino teve como objetivo avaliar a eficácia da lomustina administrada em cães acometidos por TVTC. Outro objetivo foi propor uma outra opção terapêutica nos casos em que o protocolo quimioterápico com sulfato de vincristina não for uma opção viável ao tutor do animal. Para este estudo foram selecionados 12 cães com diagnóstico citopatológico de TVTC genital, que foram submetidos ao protocolo experimental com administração de lomustina na dose de 70 a 85 mg/m2 por via oral, a cada 21 dias, totalizando no máximo dois ciclos de administrações. Os animais foram reavaliados a cada 7 dias até no máximo o dia +49 após a primeira dose da lomustina, para realização de acompanhamento da regressão das lesões neoplásicas através de mensurações e para monitoramento hematológico e bioquímico sérico para detectar possíveis efeitos adversos relacionados ao tratamento. Entre os 12 cães submetidos ao protocolo de tratamento, 8 alcançaram remissão completa da neoplasia (66,6%), 1 apresentou resposta parcial ao tratamento (8,33%) e três apresentaram doença estável (25%). Efeitos adversos importantes como intensa leucopenia neutrofílica foram detectados através de exames em 3 cães (25%). O estudo clínico permite concluir que a lomustina pode ser uma opção de tratamento para o TVTC, nos casos em que os valores do tratamento convencional sejam um fator determinante na escolha do protocolo terapêutico, contudo são necessárias avaliações hematológicas seriadas para identificar possíveis efeitos adversos devido a mielotoxicidade do fármaco. O capítulo 2 intitulado Aspectos epidemiológicos, clínicos, e terapêuticos do tumor venéreo transmissível na região do Rio de Janeiro, Brasil (2015 a 2020) teve como objetivo apresentar dados epidemiológicos e clínicos de animais diagnosticados com TVTC, ressaltando as manifestações clínicasmais observadas, os protocolos terapêuticos utilizados e suas respectivas respostas, bem como fatores epidemiológicos relacionados à transmissão e o desenvolvimento da doença na cidade do Rio de Janeiro e região metropolitana. O estudo concluiu que o TVTC apresenta elevada ocorrência na região, com apresentações clínicas mais frequentes em região genital, contudo foi observada elevada casuística de tumores extragenitais. O sulfato de vincristina foi o principal tratamento utilizado e é eficaz em induzir remissão da neoplasia, porém foi observado que 40% dos cães acometidos não são tratados por opção dos tutores. O capítulo 3 Aspectos clínicos e citopatológicos da remissão espontânea de tumor venéreo transmissível canino relato de caso traz a descrição de um caso de remissão espontânea de TVTC e teve como objetivo enfatizar os aspectos clínicos e citopatológicos observados durante o curso da regressão. O relato permitiu observar um raro caso de remissão espontânea de TVTC de ocorrência natural e verificar as nuances citopatológicas associadas ao processo de regressão. O capítulo 4 Tumor venéreo transmissível canino laríngeo com metástases pulmonares relato de caso teve como objetivo realizar a descrição de um caso raro de TVTC em laringe com desenvolvimento de focos metastáticos em parênquima pulmonar e destacar o acompanhamento clínico e radiográfico durante o tratamento antineoplásico. O capítulo permite concluir que o TVTC pode se manifestar de formas atípicas, inclusive em cães impúberes e localizações anatômicas inusitadas

The canine transmissible venereal tumor (TVTC) is one of the most common neoplasms in dogs, and mainly affects animals with free access to the street, since it is transmitted predominantly through coitus. The choice treatment is through chemotherapy with intravenous vincristine sulfate, with weekly intervals and high cost, which often makes it difficult to continue the treatment for the guardians of the affected animals. Lomustine is an orally administred chemotherapeutic agent, with an interval of 21 days between applications, which facilitates treatment adherence by tutors. The study described in chapter 1 entitled "Lomustine efficacy in the treatment of canine transmissible venereal tumor" aimed to evaluate the efficacy of lomustine administered to dogs affected by TVTC. Another objective was to propose other therapeutic option in cases where the chemotherapeutic protocol with vincristine sulfate is not a viable option for the animal's guardian. For this study, 12 dogs with cytopathological diagnosis of genital TVTC were selected, who were submitted to the experimental protocol with administration of lomustine at a dose of 70 to 85 mg / m2 orally, every 21 days, totaling a maximum of two administration cycles. The animals were reassessed every 7 days until a maximum of +49 day after the first dose of lomustine, to monitor the regression of neoplastic lesions through measurements and to monitor serum hematology and biochemistry to detect possible adverse effects related to treatment. Among the 12 dogs submitted to the treatment protocol, 8 achieved complete remission of the neoplasia (66.6%), 1 had partial response to treatment (8.33%) and three had stable disease (25%). Important adverse effects such as intense neutrophilic leukopenia were detected through examinations in 3 dogs (25%). The clinical study concludes that lomustine may be a treatment option for TVTC, in cases where the values of conventional treatment are a determining factor in the therapeutic choice protocol, however serial hematological evaluations are necessary to identify possible adverse effects due to the drugs myelotoxicity. Chapter 2 entitled Epidemiological, clinical, and therapeutic aspects of the transmissible venereal tumor in the region of Rio de Janeiro, Brazil (2015 to 2020) aimed to present epidemiological and clinical data of animals diagnosed with TVTC, highlighting the most observed clinical manifestations , the therapeutic protocols used and their respective responses, as well as epidemiological factors related to the transmission and development of the disease in the city of Rio deJaneiro and the metropolitan region. The study concluded that TVTC has a high occurrence in the region, with more frequent clinical presentations in the genital region, however a high number of extragenital tumors was observed. Vincristine sulfate was the main treatment used and is effective in inducing remission of the neoplasm, however it was observed that 40% of the affected dogs are not treated at the guardians' option. Chapter 3 Clinical and cytopathological aspects of spontaneous remission of a canine transmissible venereal tumor - case report provides a case description of spontaneous remission of TVTC and aimed to emphasize the clinical and cytopathological aspects observed during the regression course. The report made it possible to observe a rare case of spontaneous remission of naturally occurring TVTC and to verify the cytopathological nuances associated with the regression process. Chapter 4 Canine laryngeal transmissible venereal tumor with pulmonary metastases - case report aimed to describe a rare case of TVTC in the larynx with development of metastasis in the lung parenchyma and to highlight the clinical and radiographic monitoring during antineoplastic treatment . The chapter allows us to conclude that TVTC can manifest in atypical ways, including in impudent dogs and unusual anatomical locations.

Alterações metabólicas e endocrinológicas relacionadas ao eixo hipotálamohipófise-adrenal em cães com mastocitoma: comparação de diferentes protocolos de tratamento.

Na espécie canina há poucos estudos que demonstrem a ocorrência de alterações endócrinas adversas às neoplasias ou terapias antineoplásicas. Os objetivos deste projeto incluem a avaliação dos níveis de cortisol e de parâmetros metabólicos em cães com mastocitoma anterior ou posteriormente à sua terapia. Secundariamente avaliamos os efeitos do mastocitoma sobre as características ultrassonográficas de adrenais, o efeito de um fosfolipídio antineoplásico em cães com este tipo de neoplasia e fizemos uma revisão sobre o uso de glicocorticoides em cães com neoplasias. Desta forma esta tese resultou em cinco artigos científicos. O estudo principal envolveu a realização do teste de estimulação com ACTH em 44 cães com mastocitoma cutâneo ou subcutâneo anterior e 30 dias após sua terapia cirúrgica isoladamente (n=10) ou seguida de vimblastina e prednisona (n=12), lomustina e prednisona (n=12) ou fosfato de 2-aminoetildiidrogênio (n=10), que foram comparados a um grupo controle (n=10). Demonstramos que cães com mastocitoma podem apresentar elevação dos níveis de cortisol pós ACTH anteriormente à terapia e, portanto, falsos positivos para hiperadrenocorticismo, com menor ocorrência deste tipo de ocorrência após o tratamento da neoplasia. Um segundo estudo comparou o resultado de parâmetros metabólicos (peso, escore de condição corporal e níveis séricos de glicose, alanina aminotransferase, fosfatase alcalina, triglicérides, colesterol) destes 44 cães com mastocitoma e comparou estes achados entre os mesmos grupos de terapia e controle. Concluiu-se que há ocorrência de elevação de alanina aminotransferase, hiperfosfatasemia, hipercolesterolemia e hipertrigliceridemia em cães tratados com quimioterápicos associados à prednisona. Descrevemos em um terceiro artigo uma revisão bibliográfica sobre o uso de glicocorticoides sintéticos em casos de neoplasias caninas. Um quarto trabalho envolveu o estudo prospectivo do uso de fosfato de 2-aminoetil-diidrogênio em 10 cães com mastocitoma no qual demonstramos que este fármaco foi seguro nestes animais. No entanto não foi suficientemente eficaz para prevenir a recidiva de novo tumor ou metástase em cães com fatores imuno-histoquímicos de mau prognóstico. Por fim, foi realizado um estudo retrospectivo das alterações de dimensões, morfologia, ecogenicidade e presença de neoformações em adrenais de cães com mastocitoma (n=120). Observou-se adrenomegalia em 30%, alterações morfológicas de adrenais em 7,5%, neoformações adrenais em 1,6% dos casos e concluiu-se que cães com mastocitoma pode apresentar alterações principalmente nas dimensões adrenais.

In the canine specie, there are few studies that demonstrate the occurrence of adverse endocrine alterations to neoplasms or antineoplastic therapies. The objectives of this project include the assessment of cortisol levels and metabolic parameters in dogs with mast cell tumors before or after their therapy. Secondarily, we evaluated the effects of mast cell tumors on the sonographic characteristics of adrenals, the effect of an antineoplastic phospholipid in dogs with this type of neoplasm, and we reviewed the use of glucocorticoids in dogs with neoplasms. Thus, this thesis resulted in five scientific articles. The main study involved performing the ACTH stimulation test in 44 dogs with previous cutaneous or subcutaneous mast cell tumors and 30 days after their surgical therapy alone (n=10) or followed by vinblastine and prednisone (n=12), lomustine and prednisone ( n=12) or 2-aminoethyl-dihydrogen phosphate (n=10), which were compared to a control group (n=10). We demonstrated that dogs with mast cell tumors may present elevated cortisol levels after ACTH stimulation prior to therapy and, therefore, false positives for hyperadrenocorticism, with a lower occurrence of this type after treatment of the neoplasm. A second study compared the outcome of metabolic parameters (weight, body condition score and serum levels of glucose, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol) of these 44 dogs with mast cell tumors and compared these findings between the same therapy and control groups. It was concluded that there is an increase in alanine aminotransferase, hyperphosphatasemia, hypercholesterolemia and hypertriglyceridemia in dogs treated with chemotherapy associated with prednisone. In a third article, we describe a literature review on the use of synthetic glucocorticoids in cases of canine neoplasms. A fourth work involved the prospective study of the use of 2-aminoethyl dihydrogen phosphate in 10 dogs with mast cell tumors in which we demonstrated that this drug was safe in these animals. However, it was not effective enough to prevent the recurrence of a new tumor or metastasis in dogs with immunohistochemical poor prognostic factors. Finally, a retrospective study of alterations in dimensions, morphology, echogenicity and the presence of neoformations in the adrenals of dogs with mast cell tumors (n=120) was performed. Adrenomegaly was observed in 30%, morphological changes of the adrenals in 7.5%, adrenal neoformations in 1.6% of the cases and it was concluded that dogs with mast cell tumors may present mainly changes in adrenal dimensions.

Características morfológicas de tumores intra-axiais em cães por imagem de ressonância magnética

As características dos tumores gliais na imagem de ressonância magnética em cães são extremamente similares às encontradas em humanos. Mudanças sutis na imagem podem revelar uma classificação de menor ou maior grau, indicando caráter agressivo e um prognóstico sombrio ao paciente. O total de 18 cães foram submetidos ao exame de ressonância magnética (RM) do encéfalo com a utilização de contraste paramagnético e o critério de inclusão adotado para o presente estudo foi a detecção de lesões solitárias intra-axiais na imagem de RM. A partir da sugestão diagnóstica de tumor intra-axial por imagem de ressonância magnética os animais foram submetidos ao tratamento com o uso da lomustina, quimioterápico utilizado para tratamento de tumores intracranianos, associado ao tratamento de suporte convencional. Cada paciente foi monitorado clinicamente durante o período de tratamento compilando-se os sinais clínicos apresentados. Os resultados obtidos na imagem de RM demostraram que os tumores primários intra-axias sotitários apresentaram localização predominante no telencéfalo (75%) e intensificação de contraste moderada. No monitoramento clínico dos animais, referente ao protocolo terapêutico instituído, observou-se maior acometimento da raça Boxer, idade média de 8,5 anos e o sinal clínico mais relevante foi alteração de estado mental. Na análise de sobrevida identificou-se a média de 85 dias para os tumores de localização supratentoriais e 26 dias para os tumores infratentoriais. O presente estudo possibilitou obter informações específicas e maior compreensão das características dos tumores intra-axiais em cães, assim como informações dos principais sinais clínicos e da sobrevida dos animais sob monitoramento do protocolo terapêutico.

The characteristics of glial tumors in the MRI image in dogs are extremely similar to those found in humans. Subtle changes in the image can reveal a lower or higher degree of classification, thus indicating an aggressive character and a dismal prognosis for the patient. A total of 18 dogs underwent brain magnetic resonance examination using paramagnetic contrast and the inclusion criterion adopted for the present study was the detection of primary intra-axial lesions. Based on the diagnostic suggestion of an intra-axial tumor by magnetic resonance imaging, the animals were subjected to treatment using of lomustine, chemotherapy used to treat intracranial tumors, associated with conventional supportive treatment. Each patient was monitored clinically during the treatment period by compiling the clinical signs presented. The results obtained in the magnetic resonance image showed that the primary tumors of the solitary intra-axia showed a predominant location in the telencephalon (75%) and a moderate increase in contrast. In the clinical monitoring of the animals, referring to the established therapeutic protocol, a greater involvement of the Boxer breed was observed, with an average age of 8.5 years and the change in mental status was the most evident clinical sign. In the survival analysis, the average of 85 days for tumors of supratentorial location and 26 days for infratentorial tumors was identified. The present study made it possible to obtain specific information and a better understanding of the characteristics of intra axial tumors in dogs, as well as clinical information and animal survival under therapeutic protocol and clinical monitoring.

Quimioterapia metronômica como tratamento adjuvante para o mastocitoma cutâneo em cães

A quimioterapia metronômica é uma modalidade terapêutica onde o agente quimioterápico é administrado em baixas doses, em curtos intervalos e continuamente, diferente da quimioterapia em dose máxima tolerada. Dirigida contra células tumorais e outros tipos de células, como as endoteliais e do sistema imunológico, a metronômica altera o microambiente tumoral e suprime características inatas que apoiam o crescimento dos tumores. O objetivo deste trabalho foi analisar prospectivamente o uso da quimioterapia metronômica com lomustina em pacientes com mastocitoma cutâneo, seus efeitos adversos e comparar com o protocolo de vimblastina e prednisona. Para tanto foram incluídos neste estudo 40 neoplasias obtidas de 32 cães de ambos os sexos e idades variadas, com o diagnóstico citológico e histopatológico de mastocitoma cutâneo, os mesmos foram divididos em dois grupos de forma randomizada. O grupo VP foi tratado com vimblastina na dose de 2mg/m² e prednisona por 12 sessões e o grupo LP foi tratado a metronômica com lomustina na dose de 2,84mg/m²/VO por 4 meses. Quanto à classificação histopatológica dos tumores estudados 67,5% (27/40) das formações mostrou graduação intermediária, correspondendo a grau II/baixo grau. Os efeitos adversos foram avaliados de acordo com os critérios do VCOG. Dos pacientes pertencentes ao grupo VP 62,5% (5/16) apresentaram algum tipo de efeito adverso, sendo os mais frequente os efeitos sob o trato gastrointestinal como: disorexia, anorexia, êmese e diarreia ocorrendo em cinco pacientes (5/16), seguido de leucopenia em três animais (3/16). No grupo LP 50% (8/16) dos pacientes tiveram algum tipo de efeito adverso, o mais comum foi êmese, sendo que apenas um cão apresentou efeito adverso classificado em grau III. Os dois protocolos foram bem tolerados pelos pacientes e não houve significância estatística sobre os efeitos adversos de ambos os grupos (p=0,715). A trombocitose foi a síndrome paraneoplásica mais observada, acometendo 25% de todos os animais (8/32), apresentando significância estatística em relação ao temo de sobrevida global (p=0,000049). A média de sobrevida do grupo VP foi de 404,25 dias (104-815dias) enquanto que do grupo LP foi de 320,25 dias (83-669). Não houve diferença estatística entre os grupos de acordo com o tempo de sobrevida (p=0,662) e o tempo livre de recorrência (p=1). A quimioterapia metronômica com lomustina teve boa aceitação junto aos proprietários dos animais, já que é administrada por via oral e os efeitos adversos foram toleráveis e pouco frequentes.

Metronomic chemotherapy is a therapeutic modality where the chemotherapeutic agent is administered in low doses, continuously for short and regular periods, as opposed to the chemotherapy in maximum tolerated dose. Directed against tumor cells and other cell types, such as endothelial cells and immune system cells, the metronomic chemotherapy alters the tumor microenvironment and suppresses innate features that support the growth of tumors. The aim of this study is to prospectively analyze the use of metronomic chemotherapy with lomustine in patients with mast cell tumors, evaluate the therapeutic action and adverse effects and compare with the chemotherapy protocol with vinblastine and prednisone. For this, 40 neoplasms obtained from 32 dogs of both sexes and varied ages, with cytological and histopathological diagnosis of mast cell tumor, were divided into two groups in a randomized fashion. The VP group was treated with vinblastine at a dose of 2mg/m² and prednisone for 12 sessions and the LP group was treated with metronomic chemotherapy with lomustine at a dose of 2.84mg/m²/ VO for 4 months. Regarding the histopathological classification of the studied tumors, 67.5% (27/40) of the formations showed an intermediate degree, corresponding to grade II / low grade. Adverse effects were assessed according to the VCOG criteria. Of the patients belonging to the VP group 62.5% (5/16) presented some type of adverse effect, being the most frequent the effects under the gastrointestinal tract as: dysorexia, anorexia, emesis and diarrhea occurring in five patients (5/16), Followed by leukopenia in three animals (3/16). In the LP group 50% (8/16) of the patients had some type of adverse effect, the most common was emesis, and only one dog presented grade III adverse effect. The two chemotherapeutic protocols were well tolerated by the patients and there was no statistical significance regarding the adverse effects of both groups (p = 0.715). Thrombocytosis was the most observed paraneoplastic syndrome, affecting 25% of all animals (8/32), presenting statistical significance in relation to the overall survival rate (p = 0.000049). The mean survival time of the PV group was 404.25 days (104-815 days) while the LP group was 320.25 days (83-669). There was no statistical difference between the groups according to the survival time (p = 0.662) and the free time of recurrence (p = 1). Metronomic chemotherapy with lomustine was well accepted by animal owners, since it is administered orally and the adverse effects were tolerable and infrequent.

LINFOMAS CUTÂNEOS EM CÃES: ESTUDO EPIDEMIOLÓGICO, MORFOLÓGICO, IMUNOFENOTÍPICO E SEROPROTEICO

Foram analisados neste estudo 29 casos de linfoma cutâneo canino atendidos no Hospital Veterinário da Unesp (Universidade Estadual Paulista), campus de Jaboticabal, SP, Brasil. Os cães acometidos foram provenientes de 13 cidades diferentes do Estado de São Paulo; um terço não apresentaram definição racial e a média deidade no momento do diagnóstico foi de 7,8 anos. A apresentação clínica predominante das lesões cutâneas foi nódulos/tumores (86,2%), seguida por úlceras (75,8%) e placas (51,7%). Na avaliação histopatológica, a forma não epiteliotrópica foi a mais frequente (75%). Lomustina e prednisolona foramosfármacos terapêuticos de eleição (70-90mg/m2). O tempo de sobrevida média após o momento do diagnóstico foi de 26 dias. As variáveis que tiverem influência positiva (P<0,1) na sobrevida foram o epiteliotropismo e alterações hematológicas pós quimioterapia (anemia, leucopenia e trombocitopenia). Observou-se resposta desfavorável ao tratamento, progressão rápida da neoplasia e sobrevida reduzida nos 29 cães deste estudo.

This study analyzed 29 cases of canine cutaneous lymphoma attended at the Veterinary Hospital of Unesp (Universidade Estadual Paulista), Jaboticabal, SP, Brazil. Results showed that they were from 13 different cities at State of São Paulo; a third of all dogs had no racial definition and the average age at diagnosis was 7.8 years. The predominant clinical presentation of skin lesions was nodules / tumors (86.2%), followed by ulcers (75.8%) and plaques (51.7%). Histopathological evaluation revealed that the epitheliotropic form was the most frequent (75%). Lomustine was the therapeutic protocol of choice (70-90mg/m2). The average survival time after diagnosis was 26 days. The variables that had a positive influence (P <0.1) on survival were epitheliotropism and hematological alterations after chemotherapy (anemia, leukopenia and thrombocytopenia). Poor response to treatment, rapid neoplasia progression and reduced survival were observed in the 29 dogs in this study.

Quimioterapia antineoplásica em cães e gatos – uma revisão das opções de tratamento por via oral / Antineoplastic chemotherapy in dogs and cats – a review of oral treatment options / Quimioterapia antineoplásica en perros y gatos – una revisión de las opciones de tratamiento por vía oral

Apesar de a maioria dos antineoplásicos ser administrada por via intravenosa, há atualmente uma vasta disponibilidade desses fármacos apresentados em drágeas, comprimidos e cápsulas. Algumas vantagens da quimioterapia oral são a possibilidade de um tratamento prático, indolor e bem tolerado. Contudo, a prescrição de medicações citotóxicas para uso domiciliar deve ser criteriosa, para evitar que o tratamento represente risco à saúde dos animais e proprietários. Esta revisão de literatura relaciona e descreve os fármacos ciclofosfamida, clorambucil, melfalano, bussulfano, lomustina, capecitabina, metotrexato, idarrubicina, etoposídeo, mercaptopurina, anti-inflamatórios esteroides e inibidores de ciclo-oxigenase-2 e de tirosina-quinase. Esses medicamentos estão atualmente disponíveis para o uso por via oral na medicina humana e podem ser utilizados para o tratamento do câncer em cães e gatos.

Although most anticancer drugs are administered intravenously, several of these drugs are currently available as pills, tablets and capsules. Some advantages of oral chemotherapy are the possibility of a practical, painless and well tolerated treatment. However, prescription of cytotoxic medications for use at home should be done carefully to prevent risks to animal and human health. This literature review lists and describes the drugs cyclophosphamide, chlorambucil, melphalan, busulfan, lomustine, capecitabine, methotrexate, idarubicin, etoposide, mercaptopurine, steroidal anti-inflammatory, cyclooxygenase-2 and tyrosine kinase inhibitors. These drugs are currently available for oral usage in human medicine and can be used for the treatment of cancer in dogs and cats.

A pesar de que la mayoría de los antineoplásicos se presentan por vía endovenosa, existen actualmente un gran número de esos fármacos que se comercializan en forma de grageas, comprimidos y cápsulas. Algunas de las ventajas de la quimioterapia oral son la de ser un tipo de tratamiento práctico, indoloro y bien tolerado. No obstante, la prescripción de medicamentos citotóxicos para su uso en el domicilio del paciente, debe ser criteriosa, a fin de evitar que el tratamiento cause algún riesgo a los animales o al propietario. Esta revisión de la literatura relaciona y describe los fármacos ciclofosfamida, clorambucil, melfalano, bussulfano, lomustina, capecitabina, metotrexato, idarrubicina, etoposídeo, mercaptopurina, antiinflamatorios esteroides e inhibidores de la ciclo oxigenasa 2 y de tiroxina quinasa. Estos medicamentos se encuentran actualmente disponibles para su uso por vía oral en la medicina humana, y pueden ser utilizados para el tratamiento del cáncer en perros y gatos.