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.

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)

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: a novel chemotherapeutic protocol for feline high-grade multicentric or mediastinal lymphoma, developed in an area endemic for feline leukemia virus.

OBJECTIVES: The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). METHODS: This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan-Meier curves. RESULTS: Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20-31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. CONCLUSIONS AND RELEVANCE: The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.

Electrochemical behaviour of anticancer drug lomustine and in situ evaluation of its interaction with DNA.

Electrochemical techniques were used to investigate the behavior of lomustine (CCNU) and its degradation in aqueous solution at a glassy carbon electrode (GCE). The in situ interaction of CCNU and chemically degraded CCNU (cdCCNU) with dsDNA was then investigated in dsDNA incubated solutions, using dsDNA electrochemical biosensors and comet assays. CCNU undergoes electrochemical reduction in two irreversible, diffusion-controlled, and pH-dependent redox processes, each with transfer of two electrons and one proton. At pH ≥ 10.1, the peak potential for the two processes was essentially pH-independent and involved only one electron. A mechanism was proposed for the reduction of CCNU in a neutral medium. In addition, it was found that CCNU underwent spontaneous degradation during incubation in aqueous solution, without the formation of electroactive degradation products. The degradation process was faster in basic media. Moreover, this pro-drug interacted with the DNA. Its metabolite(s) initially caused condensation of the double helix chains, followed by the unwinding of these chains. In addition, free guanine (Gua) was released from the dsDNA and oxidative damage to the DNA by the CCNU metabolite(s) was evidenced from the detection of 8-oxoGua and 2,8-oxoAde. These results were confirmed by the poly(dA)- and poly(dG)-polyhomonucleotide biosensors, which revealed the oxidative damage caused to both bases (guanine and adenine) of the dsDNA by the CCNU metabolite(s). The comet assay indicated breaks in the single strand DNA, complementing the results of the studies using differential pulse voltammetry. Conformational changes of dsDNA caused by CCNU and cdCCNU were confirmed using comet assays.

OIP5 Expression Sensitize Glioblastoma Cells to Lomustine Treatment.

Glioblastoma (GBM) is an incurable disease ranked among the deadliest solid cancers worldwide. A better understanding on the molecular aspects of this malignancy could contribute to the development of new treatment strategies and help to improve survival rates. Previously, our group had shown that GBM patients expressing the cancer/testis antigen Opa Interacting Protein 5 (OIP5) present a longer survival period than the OIP5-negative group. The main goal of this study was to evaluate the OIP5 contribution to GBM tumorigenesis and assess the role of OIP5 in GBM cell response to lomustine, an alkylating agent used in the treatment of this malignancy. So, the effect of OIP5 knockdown was evaluated in A172 and T98G GBM cell lines. Our results demonstrated that downregulation of the OIP5 stimulates glioma cell viability and inhibits cell death-induced necrosis prompted by lomustine. In conclusion, our data shows that OIP5 expression in GBM cells seems to be able to enhance lomustine cytotoxic effects, reinforcing that this gene is a potential therapeutic target and putative molecular biomarker for treatment response in GBM.

Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine.

PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance. METHODS: We studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl2) on the effects of both drugs was evaluated. RESULTS: During the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl2-induced MMR deficiency increased cytotoxicity of CCNU. CONCLUSION: Our results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.

Hepatotoxicidad colestásica asociada al uso de quimioterapia en esquema con lomustina: reporte de un caso y revisión de la literatura / Colestasic hepatotoxicity associated with the use of chemotherapy in scheme with lomustine: case report and literature review

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.

Cutaneous lymphoma of the tarsus in a cat - case study / Linfoma cutáneo tarsal en gato - estudio de caso

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.

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)

Avaliação da mielotoxicidade induzida pelo uso da lomustina (CCNU) em cães durante o tratamento para mastocitoma / Evaluate of the myelotoxicity induced by lomustine (CCNU) in dogs during treatment for mast cell tumor

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)

Avaliação da mielotoxicidade induzida pelo uso da lomustina (CCNU) em cães durante o tratamento para mastocitoma / Evaluate of the myelotoxicity induced by lomustine (CCNU) in dogs during treatment for mast cell tumor

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 didn’t 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