Hemorrhagic diathesis and bone marrow aplasia secondary to lomustine overdose in a dog.

A 9-year-old mixed breed 13 kg spayed female dog was presented for evaluation of two masses in the right abdominal mammary gland region. Surgery was conducted to excise the masses. A grade I complex mammary gland carcinoma and high grade (grade III) mast cell tumor with an inguinal lymph node metastasis were diagnosed. Forty-seven days after the surgical procedure, the mast cell tumor relapsed, and neoadjuvant treatment with lomustine (81 mg/m2 ) was prescribed. Thirteen days from initiation of lomustine therapy, the dog was re-presented to the hospital with bloody diarrhea, hematemesis, epistaxis, an elevated rectal temperature, depression, severe dehydration, and marked dyspnea. The CBC showed severe thrombocytopenia and leukopenia. According to the owner, lomustine (45mg per os [PO]) was mistakenly administered daily for 10 consecutive days (total dose, 810 mg/m2 ). The dog died and a necropsy was performed. The main gross lesions consisted of severe multifocal hemorrhages in multiple organs, especially in the digestive system. Histopathologic evaluation revealed disseminated hemorrhages, as well as marked bone marrow aplasia. This report describes the clinical, hematologic, gross, and histologic findings in a fatal case of lomustine overdose in a dog.

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.

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)

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...

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...

Patients with primary brain tumors.

The purpose of this prospective phase II/III trial was to study the effect of therapy intensification when combining procarbazine, lomustine, and vincristine (PCV) chemotherapy with a standard course of radiation therapy (RT) on cognitive functioning for patients with World Health Organization grade 2 low-grade gliomas (LGGs). Initial results of the trial demonstrated a progression-free survival benefit with adjuvant PCV, but no overall survival benefit in the intention-to-treat analysis. Because patients with LGGs have favorable prognostic indicators, the five-year overall survival rates range from 60%-70%. The effect of cancer treatment on neurocognitive function is a topic of increasing interest to healthcare providers and patients. The negative effect is commonly called "chemobrain" and refers to diminished concentration and compromised short-term memory following treatment. Chemobrain has been studied in other populations of patients with cancer (e.g., breast cancer) with associated statistically significant chemotherapy-associated compromised cognitive function when chemotherapy was added to RT.

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

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)