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Background: Thyroid tumor is a common endocrine tumor that accounts for up to 3.8% of all tumors in dogs. Most of them are malignant and usually nonfunctional in dogs. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging modality that detects intracellular accumulation of radioactive deoxyglucose administered in the body and is used in combination with computed tomography to provide functional information with exact anatomical localization. It is used in human medicine to detect residual or recurrent head and neck neoplasm after treatments, such as surgical resection. This report describes the first case of diagnosing recurrent thyroid carcinoma (TC) through FDG-PET in a dog. Case: A 9-year-old castrated male Maltese dog presented with a palpable mobile mass in the right ventral cervical region. Radiography and ultrasonography (US) showed a radiopaque mass adjacent to the trachea, and the right thyroid gland was enlarged on computed tomography. The surgically excised mass was encapsulated and measured to be 2.3 × 1.0 × 3.4 cm (width x length x height) in size. Histopathologically, the mass was diagnosed as differentiated follicular TC, and gross and vascular invasions were observed. To prevent recurrence, postoperative carboplatin chemotherapy was performed for 5 months. Two months after completion of chemotherapy, a nodule of approximately 7 mm in diameter was detected in the thyroidectomy bed by US. FDG-PET scanning was performed as an effective means of evaluating the malignancy, local recurrence, and metastasis of differentiated follicular TC. The nodule had the dimensions of 2.8 × 5.9 × 8.6 mm, a maximum standardized uptake value (SUV) of 8.49, and a mean SUV of 5.6. The results of FDG-PET suggested the recurrence of TC; therefore, the second chemotherapy protocol using toceranib was applied for 16 months. After initiation of the 2nd chemotherapy, follow-up examinations were conducted approximately every 4 months. On the 134th day, although the nodule was not palpated, its size was observed to have increased to 5.0 × 3.8 × 13.6 mm on cervical US on the 232nd day, showing heterogeneous and hypoechoic parenchyma. On the 405th day, the tumor was enlarged to a size of 13.4 × 12.9 × 22 mm and identified as a lobular, amorphous shape, and its heterogeneity was increased. Moreover, 2 pulmonary nodules with well-defined margins were found on radiography in the left caudal lung lobe (9 × 10 mm and 12 × 12 mm [width × length]); thus, lung metastasis was suspected. On the 536th day, anorexia and lethargy occurred, and the dog was lost to follow-up. Discussion: In the present case, local recurrence of TC was suspected based on cervical US. Although US was useful as a screening tool, additional examinations were necessary for evaluating local invasiveness, malignancy, and nodal/distant metastasis. FDG-PET can detect recurrence at an early stage because it can sense increased tumor metabolism through physiologic absorption of FDG, even before the beginning of anatomic change in the lesion. Therefore, FDG-PET can assist in treatment planning and provide better prognosis. In humans, focal FDG uptake and a high maximum SUV in the thyroid gland on FDG-PET were associated with a higher risk of cancer. Because there was no evidence of neoplasia except the thyroid lesion during the FDG-PET examination, the tumor showed an increasingly malignant pattern of the thyroid gland on US during the follow-up period, and the metastatic pulmonary nodules were identified on the 650th day after the thyroidectomy, the present case was diagnosed as recurrent TC. This report describes the use of FDG-PET for diagnosing local recurrence of TC, pointing to FDG-PET as a potential strategy to evaluate loco-regional recurrence and distant metastasis of TC.

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Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

As neoplasias mamárias representam o tipo de neoplasma mais frequentemente diagnosticado em fêmeas da espécie canina. Embora a remoção cirúrgica seja o procedimento de eleição para a conduta terapêutica, os protocolos quimioterápicos aparecem como importantes aliados e adjuvantes. Apesar dos grandes avanços ocorridos na área da terapia oncológica, as repercussões sistêmicas destes fármacos ainda impõem importantes limitações ao seu uso. Neste sentido, o desenvolvimento de protocolos terapêuticos cada vez mais direcionados e o monitoramento preventivo dos pacientes representam estratégias importantes para evitar possíveis complicações - dentre elas, a injúria renal aguda (IRA). Rotineiramente, a avaliação ultrassonográfica é utilizada para identificação de variações morfológicas ou metastáticas em órgãos da cavidade abdominal. Atuando de forma complementar à avaliação em modo-B, o mapeamento Doppler mostra-se eficiente no reconhecimento de alterações na hemodinâmica vascular. Portanto, o objetivo do presente estudo foi avaliar a utilização da ultrassonografia modo-B e Doppler como método para identificação de alterações morfológicas e hemodinâmicas renais em cadelas com neoplasias mamárias submetidas a protocolos quimioterápicos adjuvantes que associam a gencitabina à carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto a raça e com idades entre sete e 13 anos. Os animais foram avaliados ultrassonograficamente em dois momentos distintos durante três ciclos quimioterápicos consecutivos: antes (T0) e uma hora e meia após a realização de cada ciclo (T1), totalizando 42 dias. Não foram observadas alterações morfológicas em modo-B ao longo do protocolo quimioterápico. Entretanto, os índices dopplervelocimétricos demonstraram diferenças estatísticas antes (T0) e após (T1) a administração dos fármacos. Concluiu-se que a ultrassonografia Doppler pode ser utilizada como método complementar para o monitoramento da resposta renal de pacientes expostos a fármacos nefrotóxicos e potencialmente causadores de injúrias renais.

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Background: Urethral tumors are uncommon in canines, represented predominantly by transitional cell carcinoma, marked by aggressive behavior associated with short life expectancy. Definitive diagnosis is achieved by histopathological analysis. Surgery associated with chemotherapy is the main therapeutic alternative. The aim of this paper is to report a case of primary transitional cell carcinoma of the urethra in a bitch, submitted to surgical treatment associated with conventional adjuvant chemotherapy and metronomic chemotherapy, achieving survival of 21 months, to date. Case: A 12-year-old bitch mixed breed was admitted at the Veterinary Hospital of Federal Rural University of Rio de Janeiro (UFRRJ), manifesting hematuria and urinary incontinence for one month. Physical examination indicated that vital parameters were within normal limits. Laboratory tests of blood count and serum biochemistry, urinalysis, culture, urinary antibiogram, and abdominal ultrasound were performed. The ultrasound image suggested a neoplastic urethral process. Because of the suspicion of neoplasm, a thoracic X-ray was performed, showing no evidence of metastasis. Computed tomography (CT) of the abdominal region was performed, revealing an expansive lesion in the urethra with loss of definition of the walls and urethral lumen extending to the level of the pelvic floor, measuring about 2.9 x 1.4 x 1.2 cm. After preanesthetic exams, the animal underwent resection and surgical anastomosis of the affected urethral region. The sectioned tissue was sent for histopathological analysis, with diagnosis of transitional cell carcinoma. Adjuvant chemotherapy was performed using carboplatin at a dose of 250 mg/m², intravenously, every 21 days for 6 sessions. After completing the protocol, abdominal ultrasonography was performed again, which showed a cicatricial process in the urethral region of the surgical excision, with no sign of tumor recurrence. A metronomic chemotherapy protocol was then started with cyclophosphamide at a dose of 15 mg/m², daily for 6 months, with periodic oncological follow-up. At the end of the period, the animal remained under periodic follow-up with ultrasound exams performed at 2-month intervals, and has been free from recurrence for 21 months until now. Discussion: Urethral neoplasms account for 0.5 - 2% of all canine tumors, and are represented mostly by transitional cell carcinomas. Clinical signs of urinary obstruction and hematuria are the most common, as reported in the patient in question. The definitive diagnosis is by histopathological examination. However, imaging tests such as computed tomography are important in the initial investigation and surgical planning. The indicated treatment is surgical resection of the mass with subsequent adjuvant chemotherapy or radiotherapy. The chemotherapy protocol associating cisplatin and piroxicam can achieve remission rates of 70%, but this association has a high nephrotoxic effect. In the present case, cisplatin was replaced by carboplatin in order to reduce the nephrotoxic effects of chemotherapy. The metronomic protocol using cyclophosphamide was used as maintenance therapy, at the end of the conventional chemotherapy protocol. Survival achieved was longer than that described in the literature in cases of transitional cell carcinomas in the urethral region. Therefore, multimodal therapy using surgery associated with conventional and metronomic chemotherapy, is an option in canines with urethral carcinoma.

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In breast cancer treatment, chemotherapy resistance is a major problem where many receptive tumors rebound and develop resistance. When provided in combination, cancer drugs are most successful, thus reducing the risk of developing resistant cancer cells. However, the evaluation of combination therapies has increased rapidly in recent years. Consequently, by repurposing old treatments, the discovery of additional medicines that may interact synergistically with chemotherapy is considered a current medical aim through discovering a new cancer medication or therapeutic strategy. The purpose of this research is to increase the anti-cancer activity of carboplatin (CP) by increasing the apoptotic effect of breast cancer cells (MCF-7) during in vitro experiments in combination with oxytetracycline. Our results showed a high synergistic effect between oxytetracycline and carboplatin, MCF-7 representative cell treated with carboplatin with/without different concentrations of oxytetracycline (5% and 10% of IC50). Oxytetracycline, which potentiated the action of carboplatin and/or had notable activity was reported as a single agent. This research demonstrated the synergistic relationship between oxytetracycline and carboplatin in viability assays. Surprisingly, our findings suggest that inhibiting treatment strategies can extend carboplatin's therapeutic window, potentially allowing for cancer therapy.(AU)

No tratamento do câncer de pulmão a resistência à quimioterapia é o maior problema no qual muitos tumores receptivos apresentam um rebote e desenvolvem a resistência. Quando oferecidas em combinações, as drogas anticancerígenas apresentam maior taxa de sucesso, reduzindo assim o risco de desenvolvimento de células cancerígenas resistentes. Contudo, a avaliação das terapias de combinação tem crescido muito rapidamente. Consequentemente, por reaproveitamento de tratamentos antigos, a descoberta de novos medicamentos adicionais que podem interagir sinergicamente com a quimioterapia que é considerada como auxílio médico na corrente busca à descoberta de novas medicações anticancerígenas ou estratégias terapêuticas. O propósito da presente pesquisa é aumentar a atividade anticancerígena da Carboplatina (CP) pelo incremento do efeito apoptótico de células de câncer pulmonar (MCF-7) em experimentos in vitro pela combinação com oxitetraciclina. Os resultados obtidos confirmaram elevado efeito sinérgico entre oxitetraciclina e Carboplatina em células MCF-7 representativas tratadas com Carboplatina, com e sem diferentes concentrações de oxitetraciclina (5% e 10% de IC50). A oxitetracilina que potencializou a ação da Carboplatina e/ou teve uma notável atividade relatada como um agente isolado. A pesquisa demonstrou a relação sinérgica entre oxitetraxiclina e Carboplatina nos ensaios de viabilidade. Surpreendentemente, os resultados obtidos sugeriram que as estratégias de tratamento inibidor podem aplicar um janela terapêutica da Carboplatina com potencial para a terapia do câncer.(AU)

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Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM)has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thusthe prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment whichcombines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electricalpulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosedas perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs notedwere tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m2, intravenously), administered over 20min and cisplatin intratumorally (1 mg/cm3, equivalent to 1 mL/1cm3 total volume 20 mL) administered in the upper partsof the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses,(100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system,with tumor size of 5.0 x 5.0 cm (65.4 cm3). A second ECT session was performed with the same previous protocol, butwith a decreased dosage of carboplatin (240 mg/m2 consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then...

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This report describes a pleomorphic lobular carcinoma (PLC) case, in an eight-year-old, female Shih Tzu dog, which attended the Veterinary Hospital of the University of Franca, Brazil. A single irregular, non-ulcerated, nonhyperaemic soft nodule, 2 cm in diameter, was observed during the clinical examination. The nodule was adhered within the deep tissues in the right caudal thoracic mammary gland. After removal of the nodule, the histopathologic examination showed that the neoplastic epithelial cells were scattered throughout the stroma in linear patterns, had abundant eosinophiliccytoplasm, eccentric nuclei and cytoplasmatic vacuoles, features compatible with the diagnosis of pleomorphic lobularcarcinoma. An immunohistochemical evaluation was performed in order to better characterise the tumour. Based on thenegative immunoreactivity for hormone receptors and human epidermal growth factor receptor-2 and positive expression for one of the basal markers, the basal-like triple-negative phenotype was characterized. The treatment indicated was chemotherapy with carboplatin; however, the disease progressed, and the patient had an overall survival of 47 days after surgery, confirming the aggressiveness of the disease.

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Background: The lung-digit syndrome is a rare syndrome characterized by the presence of a primary pulmonar neoplasiamanifesting metastasis to the digit, occurring exclusively in felines. The diagnosis is based on the clinical signs, associatedwith radiographic and histopathological exams. There are no therapeutic protocols well-established, and surgical excisionis considered controversial due to high recurrence and metastasis rates. The prognosis is considered poor, with low survivalrates. The aim of this paper is to report a case of lung-digit syndrome attended in Rio de Janeiro.Case: A 12-year-old female cat, no defined race, was attend with the complaint of weight loss and injury in the right thoraciclimb, already having histopathological diagnosis of squamous differentiation adenocarcinoma through biopsy. Physicalexamination showed no other clinical signs at first, including no signs of respiratory disease. Laboratory and imaging examswere performed, and the radiographic examination showed alterations in the pulmonary parenchyma showing a nodulararea of increased radiographic density. Followed up by the manifestation of breathing noise at rest, as the first respiratorysigns. The association of the clinical evaluation, medical history, and histopathological report from the limb lesion, leadto the suspicion diagnostic of lung-digit syndrome. The owners decide for the palliative treatment with chemotherapy, using carboplatin and prednisolone. Only the first session was performed, with the animal being euthanized due to clinicalworsening 48 days after the initial manifestation of clinical signs. The diagnosis was confirmed...

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ABSTRACT: The present study aimed to evaluate the use of aqueous wheat extracts as an adjunct to antineoplastic therapy with carboplatin. In this study, 32 rats were used which were randomly distributed into 4 groups: G1 - negative control; G2 - control treated with physiological solution; G3 - animals treated with aqueous extract of wheat in the concentration of 100mg/kg; G4 - animals treated with aqueous wheat extract at the concentration of 400mg/kg; 300mg/m² of carboplatin was administered intraperitoneally at day 0 in animals from groups G2, G3, and G4, whereas 1ml of physiological solution was administered by the same route in animals from group G1. Animals were treated daily for 21 days by orogastric gavage according to their respective experimental group. Blood was collected from animals on days 3, 7 and 21 for complete blood count (CBC), biochemistry, and measurement of paraoxonase 1 (PON1) activity. On day 21, animals were euthanized and necropsied. Promising results were obtained regarding oxidative balance in groups G3 and G4. Both presented better PON1 activity in comparison with group G2 (P<0.05). Total leukocyte count of group G4 differed significantly from group G2 (P<0.05) on day 21. Myelogram values of animals from groups G3 and G4 were ​​similar to those from G1; animals from G3 had lower numbers of promyelocytes and increased numbers of erythrocytes and rubriblasts than animals from G2 (P<0.05). In the present experimental study, aqueous wheat extract was safe at the doses used in the animals, and was an effective treatment for myelosuppression and for the prevention of an excessive release of free radicals induced by carboplatin.

RESUMO: O presente estudo avaliou a utilização dos extratos aquosos de trigo como adjuvante a terapia antineoplásica com carboplatina. No estudo foram utilizadas 32 ratas, as quais foram aleatoriamente distribuídas em quatro grupos: G1 - controle negativo; G2 - controle tratado com solução fisiológica; G3 - tratado com extrato aquoso de trigo na concentração de 100mg/kg; G4 - tratado com extrato aquoso de trigo na concentração de 400mg/kg. Administrou-se 300mg/m² de carboplatina por via intraperitoneal no dia 0 nos grupos G2, G3, e G4, enquanto no G1 foi administrado 1mL de solução fisiológica pela mesma via. Os animais foram tratados diariamente durante 21 dias por gavagem orogástrica de acordo com seu respectivo grupo experimental. Foi coletado sangue dos animais nos dias três, sete e 21, para realização de hemograma, testes bioquímicos e mensuração da atividade da paraoxanase 1 (PON1). No dia 21 os animais foram eutanasiados e realizada coleta de medula óssea, rim e fígado. Foram observados resultados promissores com relação ao balanço oxidativo no G3 e G4, pois ambos apresentaram melhor atividade da PON1 em relação ao G2 (P<0,05). Além disso, foi constatado que os mesmos grupos apresentaram contagem de leucócitos totais superiores ao G2 durante todo o período experimental, com G4 diferindo significativamente do G2 (P<0,05) no dia 21. Os mielogramas dos animais do G3 e G4 apresentaram valores análogos ao G1, sendo que o G3 apresentou menor contagem de promielócitos e maior de células eritroides e rubroblastos que o G2 (P<0,05). Nas condições experimentais deste estudo os extratos aquosos de trigo mostraram-se seguros nas doses utilizadas e úteis no tratamento da mielossupressão e liberação excessiva de radicais livres induzidas pelo fármaco carboplatina.

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Background: Thymomas are epithelial neoplasms of the thymus, although lymphocyte infiltration is common. Histological features are not sufficient to define its biological behaviour, which is dependent of clinical criteria of invasiveness and resectability. Myasthenia gravis may happen as a paraneoplastic syndrome in up to 47% of canine thymomas. This article aims at reporting a case of thymoma associated with myasthenia gravis in a dog, emphasizing the morphological, phenotypical and therapeutical aspects.Case: A 7-year-old, male Labrador, was presented with a history of acute dyspnea and exercise intolerance. The physical examination revealed a “red-brick” mucousa, tachycardia and cardiac and pulmonar hypofonese. Chest radiographs revealed an area of increased radiopacity in the cranial mediastinum without a plane of separation to the heart. The eccodopplercardiogram exam identified a poorly delimited mass adjacent to the base of the heart, measuring 9.5x6.8cm. Computed tomography demonstrated it as an expansive neoformation (9.5x6.5x7.8cm). Mass was removed through intercostal thoracotomy and the removed tissue was submitted to histopathology with a diagnosis compatible with type AB thymoma (mixed). Immunohistochemistry was positive for AE1/AE3 citokeratin in 90% of epithelial cells, confirming tumour origin. Tumour infiltrating lymphocytes were positive for CD79a (70%) and CD3 (20%). The proliferation index (Ki-67 imunolabeling) was 60%. About 45 days after surgery the patient was presented with generalized muscle weakness and regurgitation, with confirmed megaesophagus on chest X-ray. Treatment with pyridostigmine was initiated because of suspected myasthenia gravis, and complete remission of the neurological signs occurred within a month. A chemotherapeutic protocol with carboplatin was then instituted. After four sessions, a new thoracic radiograph revealed tumour recurrence in the cranial mediastinum.[...]

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Our retrospective study evaluated the survival of 24 dogs with unresectable malignant melanoma treated with radiation therapy. Fifteen dogs were treated with radiation therapy (RT) and chemotherapy (CT), five with surgery followed by RT and CT, three with palliative RT, and one with electrochemotherapy associated with RT. All dogs were treated with an orthovoltage Stabilipan I. The protocol used was three or four weekly fractions of 8 Gy. Carboplatin was administered every 21 days, a total of four times. Five percent of dogs were classified as having stage I melanoma, 17% as stage II, 50% as stage III, and 17% as stage IV. Sixty-four percent had a partial response to treatment, 29% achieved complete remission, and 7% remained in a stable disease state. The mean survival time was 390 days for stage I, 286 days for stage II, 159 days for stage III, and 90 days for stage IV. We concluded that radiation therapy can be considered a viable alternative for the palliative treatment of canine oral melanoma.

O estudo retrospectivo analisou a sobrevida de 24 cães com melanomas irressecáveis tratados com radioterapia (RT). Quinze animais foram tratados com RT e quimioterapia (QT), 5 animais com cirurgia citoredutiva seguida por RT e QT, 3 animais com RT paliativa apenas e 1 animal com RT associada a 1 sessão de eletroquimioterapia. Os animais foram tratados com um equipamento de ortovoltagem Stabilipan I, e o protocolo foi de três a quatro frações semanais de 8 Gy. A quimioterapia consistiu de carboplatina administrada a cada 21 dias em um total de 4 aplicações. Apenas um animal (4%) foi classificado em estadio I, enquanto quatro (17%) estavam no estadio II, doze (50%) estavam no estadio III e quatro (29%) estavam no estadio IV. De maneira geral, 64% dos cães apresentaram resposta parcial, 29% remissão completa e 7% doença estável. O tempo médio de sobrevida foi de 390 dias no estádio I, 286 dias no estádio II, 159 dias no estádio III e 90 dias no estádio IV. A radioterapia deve ser considerada pelo clínico veterinário como alternativa para o tratamento de melanoma oral canino.

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Background: Clients who seek veterinary care for pets with cancer are often concerned about the potential negative impact of chemotherapeutic treatments on their animals’ quality of life. A consensus currently exists in veterinary oncology regarding the quantification and rating of adverse treatment effects in dogs and cats in response to chemotherapy agents. This grading system is referred to as Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events. The purpose of this retrospective case series was to investigate the delayed acute effects of chemotherapy drugs in cats receiving cancer treatment.Materials, Methods & Results: Medical records were reviewed to determine the chemotherapy agent used and delayed adverse effects. Side effects were classified according to Veterinary Co-operative Oncology Group grading. All cats were evaluated after the first chemotherapy administration, after a single dose. The reported effects included hematologic effects (e.g., neutropenia, thrombocytopenia, increases in liver enzymes, and azotemia), gastrointestinal effects (e.g., vomiting, diarrhea, and inappetence), and sepsis. All of the cats in this study received ondansetron and omeprazol in the first five days following chemotherapy administration. If vomiting occurred with oral medication, maropitant was administered subcutaneously for three consecutive days. If diarrhea (> grade II) occurred, probiotics were administered for seven days. Hematologic examination was performed 3-14 days after chemotherapy. If neutropenia (> grade III) occurred, Human granulocyte colony stimulating factor was administered subcutaneously for three consecutive days together with prophylactic antibiotics. Lomustine, carboplatin, vincristine, doxorubicin, cyclophosphamide, mitoxantrone, and vinblastine were administered in 33%, 19%, 16%, 5%, 16%, 10% and 2% of the cases examined, respectively.[...]

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Feline Injection Site-Associated Sarcoma (FISS) is a neoplasm that implies in reduction of quality of life and overall survival in feline patients. A retrospective study of 13 cases of FISS was conducted to evaluate the efficacy of surgical treatment associated to chemotherapy with doxorubicin or carboplatin. Local recurrence occurred in all patients. Patients treated with surgery and chemotherapy presented a longer overall survival and disease-free interval when compared to those that solely received surgical treatment, although no statistical significance was observed (p= 0.3360 and 0.7506, respectively). Surgery remains as the main option for FISS treatment. Further prospective studies with larger samples are warranted to investigate the benefit of chemotherapy for this neoplasm.(AU)

O Sarcoma de Aplicação Felino (SAF) é uma neoplasia associada a redução na qualidade de vida e sobrevida global. O objetivo deste estudo foi avaliar a eficácia da quimioterapia associada à cirurgia no manejo do SAF. Estudo retrospectivo de 13 pacientes com SAF submetidos à cirurgia isolada ou associada a quimioterapia com carboplatina ou doxorrubicina. Recorrência local ocorreu em todos os pacientes. Pacientes tratados com cirurgia e quimioterapia apresentaram maior sobrevida global e intervalo livre de doença quando comparados àqueles que receberam apenas tratamento cirúrgico, mas não foi observada diferença estatística (p=0,3360 e 0,7506, respectivamente). A cirurgia continua sendo a principal opção para o tratamento do SAF. Estudos prospectivos são necessários para investigação do real benefício da quimioterapia para esta neoplasia.(AU)

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A quimioterapia é um dos tratamentos mais indicados para cães com neoplasias malignas. Neste estudo objetivou-se avaliar os efeitos causados pelo uso da quimioterapia em cães com tumor de mama, tratados com ciclofosfamida e carboplatina, mastocitoma tratados com vimblastina associada à prednisona e tumor venéro tansmissível (TVT) tratados com sulfato de vincristina por meio da avaliação do perfil hematológico, bioquímico sérico e urinário. Foram selecionados 20 cães, quatro com tumor de mama, nove com mastocitoma e sete com TVT. A colheita de material sanguíneo e urina foi realizados antes das sessões de quimioterapia. No grupo tumor de mama, as cadelas não apresentaram alterações hematológicas importantes, as alterações observadas foram nas enzimas ALT e AST indicando leve hepatotoxicidade, a GGT teve elevação causada pelo próprio tumor. Na função renal a creatinina, esteve aumentada até o final do tratamento, a GGT urinária também aumentou, com proteinúria na ultima sessão, acusando lesão renal tubular. No grupo mastocitoma, as enzimas ALT, AST, ALP e GGT sérica, albumina e globulinas aumentaram, indicando injúria hepática. A GGT urinária aumentou em todos os periódos, tendo proteinúria na terceira sessão, indicando lesão renal. Nos cães com TVT houve aumento nas enzimas ALT e GGT sérica em todas as sessões, indicando dano hepático. A GGT urinária aumentou na primeira e terceira sessão, a proteinúra esteve presente somente nas duas primeiras sessões. Desta forma, neste estudo as alterações mais presentes foram, hepática e renal e as enzimas GGT sérica e a GGT urinária foram importantes biomarcadores de lesão tecidual precoce em diferentes neoplasias.

Chemotherapy is one of the most indicated treatments for dogs with malignant neoplasms. This study aimed to evaluate the effects caused by the use of chemotherapy in dogs with breast tumors treated with cyclophosphamide and carboplatin, mast cell tumors treated with vinblastine associated with prednisone and veneral transmissible tumour (TVT) treated with vincristine sulfate through hematological profile, serum biochemistry and urinary profile. Twenty dogs were selected, four with breast tumor, nine with mastocytoma and seven with TVT. The collection of blood and urine material was performed before the chemotherapy sessions. In the breast tumor group, the bitches did not present important hematological changes, the changes observed were in the ALT and GGT enzymes, indicating hepatotoxicity. In renal function, creatinine was increased until the end of treatment, urinary GGT also increased, with proteinuria being observed in the last session, accusing renal tubular injury. In the mast cell tumor group, serum ALT, AST, ALP and GGT enzymes, albumin and lobulin increased, indicating possible liver damage. Urinary GGT increased in all periods, with proteinuria in the third session, also indicating kidney damage. In dogs with TVT, there was an increase in serum ALT and GGT enzymes in all sessions, indicating liver damage. Urinary GGT increased in the first and third sessions, proteinuria was present only in the first two sessions. Thus, in this study, the most frequent changes were liver and kidney, and serum GGT enzymes and urinary GGT were important biomarkers of early tissue injury in different neoplasms.

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The aim of this report was to describe the clinical findings and therapeutic management of a case of papillary adenocarcinoma of the descending colon in a Beagle. The patient presented soft stools, haematochezia, tenesmus, and dyschezia. Clinical examination revealed alterations on the ultrasonographic features of the descending colon suggestive of colitis and neoplasia. Following local mass resection, histopathology analysis revealed mild lymphoplasmocytic enteritis and papillary adenocarcinoma of the colon. Enterectomy for tumoral resection and biopsy of locoregional lymph nodes were carried out. Subsequent to the surgical procedure, it was possible to confirm the previous diagnosis and the tumor was classified as intestinal intraluminal papillary adenocarcinoma, with incomplete surgical margins. Adjuvant chemotherapy was performed using carboplatin, cyclophosphamide, and piroxicam, leading to remission of clinical signs and absence of any clinical or imaging alterations compatible with the patient's previous clinical condition.(AU)

O objetivo desse relato de caso foi descrever os achados clínicos e manejo terapêutico de um caso de adenocarcinoma papilífero do cólon descendente em um Beagle. O paciente apresentou fezes amolecidas, hematoquesia, tenesmo e disquesia. Exame clínico revelou alteração de achados ultrassonográficos do cólon descendente sugerindo colite e neoplasia. Após ressecção de massa local, análise histopatológica revelou enterite linfmoplasmocito leve e adenocarcinoma papilar do cólon. Enterectomia para ressecção tumoral e biopsia das lesões locais e tumores linfonodais foram realizadas. Após procedimento cirúrgico foi possível confirmar o diagnóstico prévio e o tumor foi classificado como adenocarcinoma papilar intraluminal intestinal, com margens cirúrgicas incompletas. Quimioterapia adjuvante foi realizada utilizando carboplatina, ciclofosfamida e piroxano, levando a remissão de sinais clínicos e ausência de alterações de imagem compatíveis com situação clínica prévia do paciente.(AU)

Resumo

Os alimentos funcionais têm sido empregados como adjuvantes no tratamento do câncer de mama. Neste estudo avaliaram-se as respostas hematológicas e bioquímicas clínicas à ação de um alimento funcional administrado a cadelas com diagnóstico de neoplasia mamária maligna. Após a mastectomia, 16 cadelas foram divididas em dois grupos: suplementadas (S) e não suplementadas (NS) com um composto comercial contendo Saccharomyces cerevisiae, mananoligossacarídeos e nutracêuticos. Ambos grupos receberam tratamento quimioterápico com doxorrubicina e carboplatina, alternadamente, em intervalos de 21 dias, por oito sessões, totalizando 168 dias de tratamento. As avaliações clínicas e laboratoriais foram realizadas nos momentos de aplicação do tratamento. Os resultados dos perfis hematológico (hemograma, leucograma e plaquetograma) e bioquímico sérico (ureia, creatinina, albumina, bilirrubina total e direta, alanina aminotransferase, fosfatase alcalina e gama glutamiltransferase - GGT) foram analisados pelo teste de Kruskall Wallis. No grupo S comprovou-se elevação do peso corporal e não foram observados transtornos gastrointestinais ou outros sinais de alteração clínica ao longo do tratamento. Diferentemente no grupo NS, ocorreu perda de peso e alterações clínicas, como diarreia e vômito. No quadro hematológico, constatou-se leucopenia por linfopenia no grupo de cadelas NS e preservação do valores dentro dos parâmetros considerados normais para a espécie no grupo S. Dentre todas as variáveis da bioquímica clínica, constatou-se apenas a elevação da atividade sérica da GGT nos animais do grupo NS, sem alterações no grupo S. Conclui-se que cadelas com neoplasia mamária quando suplementadas com com alimento funcional imunoestimulante apresentam melhor condição clínica, hematológica e dos níveis bioquímicos, particularmente da GGT.(AU)

Functional foods have been used as adjuvant for breast cancer treatment of bitches. The aim of the present study was to evaluate hematological and clinical biochemistry response in female dogs diagnosed with malignant mammary tumors and supplemented with functional food. After the mastectomy, 16 bitches were divided into two groups: supplemented (S) and none supplemented (NS) with a commercial product of Saccharomyces cerevisiae, mannanoligosaccharides and nutraceuticals. Chemotherapy with doxorubicin and carboplatin was performed alternately at intervals of 21 days for eight sessions during 168 days of treatment. Clinical and laboratorial assessments was made at the treatment moments. The results of the hemogram (erythrogram, leukogram and platelet count) and serum biochemistry (urea, creatinine, albumin, total and direct bilirubin, alanine aminotransferase, alkaline phosphatase and gamma glutamyltransferase - GGT) were analyzed by Kruskal Wallis test. In the S group, increase body weight was observed, but gastrointestinal disorders or other clinical disorders were not detected over the treatment. In the NS group, loss of weight and clinical disorders were observed. All hematology parameters were normal in the S group; however, leukopenia and lymphopenia were detected in the bitches of the NS group. Among all the clinical biochemistry parameters tested, only serum GGT was increased in the NS group, with no changes in the S group. In conclusion, female dogs with mammary tumor supplemented with immunostimulant functional food have better clinical condition, they demonstrate normal levels of hematological and biochemical exams, particularly GGT.(AU)

Resumo

As neoplasias mamárias em cadelas têm grande importância na rotina clínica de pequenos animais devido a sua elevada ocorrência. Em média 50% delas têm características de malignidade, o que faz com que a quimioterapia seja cada vez mais empregada. O uso da gencitabina associada a carboplatina é recomendado, mas apesar de auxiliarem na sobrevida do animal, também são agentes citotóxicos e podem ter efeitos secundários, como hepatotoxicidade. Detectar precocemente alterações morfológicas e hemodinâmicas hepáticas é fundamental para monitorar a resposta do paciente ao tratamento e para a manutenção do bem-estar dos animais. Desse modo, o objetivo deste estudo foi avaliar por meio da ultrassonografia em modo B e Doppler as alterações morfológicas e hemodinâmicas no fígado e na veia porta, respectivamente, de cadelas submetidas à quimioterapia adjuvante com gencitabina associada a carboplatina. Foram avaliadas 15 cadelas em três momentos (C0, C1 e C2), sendo o momento C0 o controle, realizado antes de iniciar a primeira sessão de quimioterapia; os momentos C1 e C2 foram realizados imediatamente antes da segunda e da terceira sessão de quimioterapia, respectivamente. Nos momentos preconizados (C0 a C2) foram feitos exames laboratoriais, como hemograma e bioquímica sérica. Os resultados mostraram que 33% (5/15) das cadelas apresentaram reações adversas aos fármacos, como diarreia, perda de apetite e vômitos. Apenas 20% (3/15) dos animais avaliados tiveram aumento gradual das enzimas hepáticas (ALT e FA), sem alterações significativas entre os ciclos (p>0,05). Na ultrassonografia em modo B foi encontrado aumento de ecogenicidade hepática em 27% (4/15) das cadelas no C1 e C2, ecotextura heterogênea em 13% (2/15) no C1 e C2 e dimensões hepáticas aumentadas em 20% (3/15) no C1 e C2. Não foram encontradas alterações na direção do fluxo ou nos parâmetros dopplervelocimétricos na veia porta das cadelas, nos ciclos avaliados, mesmo quando foram consideradas faixas de peso corpóreo. Concluiu-se que o protocolo com gencitabina e carboplatina não foi capaz de causar injúria hepática grave nos dois primeiros ciclos, no entanto, as alterações observadas no presente estudo sugerem que isto pode ocorrer nos tratamentos que adotem um número maior de ciclos. A ultrassonografia modo B e Doppler devem ser incluídas no monitoramento de animais submetidos ao protocolo com gencitabina e carboplatina por auxiliar na detecção precoce de alterações hepáticas.

Mammary neoplasms in bitches are of great importance in the clinical routine of small animals due to their high occurrence. On average 50% of them have malignant characteristics, which means that chemotherapy is increasingly used. The use of gemcitabine associated with carboplatin is recommended, but although they help the animal's survival, they are also cytotoxic agents and can have side effects, such as hepatotoxicity. Early detection of liver morphological and hemodynamic changes is essential to monitor the patient's response to treatment and to maintain the animals' well-being. Thus, the aim of this study was to evaluate, through B-mode and Doppler ultrasound, the morphological and hemodynamic changes in the liver and portal vein, respectively, of bitches undergoing adjuvant chemotherapy with gemcitabine associated with carboplatin. Fifteen bitches were evaluated in three moments (C0, C1 and C2), C0 was the control, performed before starting the first chemotherapy session; C1 and C2 were performed immediately before the second and third chemotherapy sessions, respectively. At the recommended moments (C0 to C2) laboratory tests were performed, such as blood count and serum biochemistry. The results showed that 33% (5/15) of the bitches had adverse drug reactions, such as diarrhea, loss of appetite and vomiting. Only 20% (3/15) of the animals evaluated had a gradual increase in liver enzymes (ALT and FA), with no significant changes between cycles (p>0.05). B-mode ultrasound showed an increase in liver echogenicity in 27% (4/15) of bitches in C1 and C2, heterogeneous echotexture in 13% (2/15) in C1 and C2 and increased liver dimensions in 20% (3/15) in C1 and C2. No changes were found in the flow direction or in the doppler velocimetric parameters in the portal vein of the bitches, in the evaluated cycles, even when body weight ranges were considered. In conclusion, the protocol with gemcitabine and carboplatin was not able to cause severe liver injury in the first two cycles, however, the changes observed in the present study suggest that this may occur in treatments that adopt a greater number of cycles. B-mode and Doppler ultrasonography should be included in the monitoring of animals submitted to the protocol with gemcitabine and carboplatin to aid in the early detection of liver alterations.

Resumo

As neoplasias mamárias representam o tipo de neoplasma mais frequentemente diagnosticado em fêmeas da espécie canina. Embora a remoção cirúrgica seja o procedimento de eleição para a conduta terapêutica, os protocolos quimioterápicos aparecem como importantes aliados e adjuvantes. Apesar dos grandes avanços ocorridos na área da terapia oncológica, as repercussões sistêmicas dos fármacos quimioterápicos ainda impõem importantes limitações ao seu uso em cães. Neste sentido, o desenvolvimento de protocolos terapêuticos cada vez mais direcionados e o monitoramento preventivo dos pacientes representam estratégias importantes para evitar possíveis complicações - dentre elas a Injúria Renal Aguda (IRA). Na medicina veterinária, a avaliação ultrassonográfica é rotineiramente utilizada para identificação de variações morfológicas ou metastáticas em órgãos da cavidade abdominal. Atuando de forma complementar à avaliação em modo-B, o mapeamento Doppler mostra-se eficiente no reconhecimento de alterações na hemodinâmica vascular. O objetivo do presente estudo foi avaliar, por meio da ultrassonografia modo-B e Doppler, as alterações morfológicas e hemodinâmicas nos rins de cadelas com neoplasias mamárias submetidas ao protocolo quimioterápico de associação entre a gencitabina e a carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto à raça e com idades entre 7 e 13 anos. Os animais foram avaliados ultrassonograficamente em dois momentos distintos durante três ciclos quimioterápicos consecutivos: antes (T0) e uma hora e meia após a realização de cada ciclo (T1). Não foram observadas alterações morfológicas em modo-B ao longo do protocolo quimioterápico, entretanto, os índices dopplervelocimétricos demonstraram diferenças estatísticas antes (T0) e após (T1) a administração dos fármacos. Concluiu-se que a ultrassonografia Doppler pode ser utilizada como método complementar para o monitoramento da resposta renal de pacientes expostos a fármacos nefrotóxicos e potencialmente causadores de injúrias renais.

Breast neoplasms is the most frequently diagnosed cancer in canine females. Although surgery is frequently the chosen procedure for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have taken place in the field of cancer therapy, the systemic repercussions of chemotherapy drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and the preventive monitoring of patients are important to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in organs of the abdominal cavity. Acting in a complementary way to B-mode assessment, Doppler mapping is efficient in recognizing changes in vascular hemodynamics. The aim of this study is to evaluate, through mode B ultrasonography and Doppler, the morphological and hemodynamic changes caused in the kidneys of those animals with breast neoplasms submitted to the chemotherapeutic protocol of association between gemcitabine and carboplatin. Altogether, 13 canine females were monitored, regardless of breed and aged between 7 and 13 years. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after the completion of each cycle (T1). Results evidenced in mode B do not indicate morphological changes along the chemotherapy protocols, however, the dopplervelocimetric indexes showed statistical differences before (TO) and after (T1) the administration of drugs. Concluded that Doppler ultrasonography can be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs that are potentially causing kidney damage.

Resumo

O melanoma é responsável pela maioria das mortes por câncer de pele, tendo alto potencial metastático, tratamento difícil e prognóstico reservado. O extrato de Viscum album (VA) é usado como terapia complementar no tratamento de pacientes oncológicos, com efeitos citotóxicos in vitro e in vivo sobre diversos tipos tumorais. No entanto, os efeitos e mecanismos de ação de preparações homeopáticas ultradiluídas do VA precisam ser melhor compreendidos. Objetivo: Assim, verificamos in vitro a ação de ultradiluições de VA em diferentes escalas de potência sobre células de melanoma murino. Métodos: Para a etapa I, tinturas mães de VA coletadas das árvores Abies alba e Quercus robur, tanto no verão quanto no inverno, foram ultradiluídas nas escalas decimal (D), centesimal (CH) e cinquenta-milesimal (LM) e em seguida submetidas a sucussão mecânica. Células de melanoma murino B16F10 foram tratadas com tintura mãe ou potências de VA na 3D, 12D, 30D, 6CH, 12CH, 200CH, 2LM, 3LM ou 5LM por 1, 24, 48, e 72 horas de incubação para análises de citotoxicidade pelos ensaios de brometo 3-(4,5-dimetil-tiazol-2-il)-2,5-difeniltetrazólio (MTT), Cristal Violeta (atividade mitocondrial e viabilidade celular, respectivamente), avaliação de marcadores de morte por apoptose (Anexina) ou necrose (7AAD), produção de espécies reativas de oxigênio (DCFH-DA), citocinas do perfil inflamatório (IFN-, TNF, IL-10, IL-6, MCP-1, IL-12p-70), e os efeitos na morfologia celular e capacidade migratória destas células tumorais após cada tratamento. Resultado: As tinturas mães de VA causaram morte das células B16F10 por necrose principalmente, com resultados similares ao do tratamento com Carboplatina. As diluições homeopáticas tiveram resultados variados, porém, com efeitos de modulação de metabolismo e viabilidade celular, aumento de necrose, redução do estresse oxidativo e diminuição da migração celular.

Melanoma is responsible for most skin cancer deaths. It has a high metastatic potential, complex treatment, and a hopeless prognosis. The Viscum album extract (VA) is a complementary treatment in oncologic patients with in vitro and in vivo cytotoxic effects against different tumor types. However, ultra-diluted homeopathic preparations' effects and mechanisms need further study. Thus, this study aims to assess the in vitro effects of ultra-diluted VA on murine melanoma. Therefore, high dilutions of VA mother tinctures harvested from Abies alba and Quercus robur trees during summer (V.Av. and V.Qv.) and winter (V.Ai. and V.Qi.) were made in decimal (D), centesimal (CH), and fifth-millesimal (LM) scales, followed by mechanical succussion. B16F10 murine melanoma cells were treated with either mother tinctures or VA potencies of 3D, 12D, 30D, 6CH, 12CH, 200CH, 2LM, 3LM, or 5LM. Cells were incubated for 1, 24, 48, and 72 hours and submitted to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity (mitochondrial activity) and violet crystal (cellular viability) tests, cell apoptosis (Anexin) and necrosis (7AAD) markers, reactive oxygens species production (DCFH-A), inflammatory cytokines (IFN-, TNF, IL-10, IL-6, MCP-1, IL-12p-70), and post treatment cellular morphology and migration capacity. VA mother tinctures caused B16F10 cells death, mostly via necrosis, with similar results as Carboplatin treatment. Homeopathic dilutions showed variable results, however, cell metabolism and viability modulation, necrosis increase, oxidative stress reduction and cell migration decrease was observed.

Resumo

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)

Resumo

MACHADO, M. C. A. Influência da ciclofosfamida na farmacocinética da carboplatina em cadelas com carcinomas mamários e graduação dos efeitos adversos decorrentes da quimioterapia. 2019. 105p. Tese (Doutor em Ciência Animal nos Trópicos) Escola de Medicina Veterinária e Zootecnia Universidade Federal da Bahia, 2019. Em virtude da importante casuística dos carcinomas mamários na cadela, se torna imprescindível estudar e propor tratamentos combinados, que favoreçam a maior eficiência terapêutica para este tipo de neoplasia, com menores efeitos adversos. Neste contexto, objetivou-se com a realização do presente estudo avaliar a influência da ciclofosfamida na farmacocinética (PK) da carboplatina em cadelas portadoras de carcinomas mamários, além de verificar possíveis efeitos adversos associados ao tratamento. Foram estudadas 16 cadelas, todas com diagnóstico histopatológico de carcinoma mamário, divididas em dois grupos experimentais, sendo o Grupo 1 constituído por cadelas tratadas apenas com carboplatina na modalidade de quimioterapia convencional (n=8) e Grupo 2 constituído por cadelas tratadas com carboplatina como quimioterapia convencional associado a ciclofosfamida em regime metronômico (n=8). Todas as cadelas foram submetidas à avaliação clínica, mastectomia, quimioterapia com carboplatina e análise da farmacocinética, além da avaliação da taxa de sobrevida e da graduação de efeitos adversos, periodicamente. Os resultados revelaram que houve diferença significativa nos parâmetros farmacocinéticos da carboplatina + ciclofosfamida (constante de eliminação (p=0,0132), meia vida (p=0,014), volume de distribuição (p=0,025), clearance (p=0,036) e área sob a curva (p=0,045)) na quarta sessão de carboplatina, com notável redução dos valores hematológicos (variáveis hemácias (p<0,0001), plaquetas (p=0,0005), leucócitos totais (p=0,0002) e neutrófilos segmentados (p=0,0007)), nas cadelas submetidas a este protocolo quimioterápico. No entanto, estes não foram suficientes para alterarem a graduação dos efeitos adversos provocados por este tipo de tratamento. Estes resultados avaliados conjuntamente indicam que a associação entre carboplatina e ciclofosfamida representa uma alternativa factível de tratamento adjuvante de cadelas com carcinomas mamários de alto grau e/ou com metástase para linfonodo regional, pois contribui para o aumento na taxa de sobrevida (p=0,0044) destas cadelas, em comparação com a carboplatina como tratamento quimioterápico único.

MACHADO, M. C. A. Influence of cyclophosphamide and pharmacokinetics of carboplatin on female dogs with mammary carcinomas and degree of adverse effects of chemotherapy. 2019. 105p. Tese (Doutor em Ciência Animal nos Trópicos) Escola de Medicina Veterinária e Zootecnia Universidade Federal da Bahia, 2019. Due to the important casuistic of the mammary carcinomas in the female dog, it is essential to study and propose combined treatments, which favor the greater therapeutic efficiency for this type of neoplasm, with lower adverse effects. In this context, the objective of this study was to evaluate the influence of cyclophosphamide on the pharmacokinetics (PK) of carboplatin in female dogs with mammary carcinomas, and to verify possible adverse effects associated with the treatment. We studied 16 female dogs, all with histopathological diagnosis of mammary carcinoma, divided into two experimental groups: Group 1 consisted of female dogs treated with carboplatin alone in the conventional chemotherapy modality (n=8) and Group 2 consisting of female dogs treated with carboplatin as conventional chemotherapy associated with cyclophosphamide in metronomic regimen (n=8). All female dogs underwent clinical evaluation, mastectomy, chemotherapy with carboplatin, and pharmacokinetic analysis, as well as the evaluation of survival rate and adverse effect score periodically. The results showed that there was a significant difference in the pharmacokinetic parameters of carboplatin + cyclophosphamide (elimination constant (p=0.0132), half-life (p=0.014), volume of distribution (p=0.025), clearance (p=0.0005), and area under the curve (p=0,045)), with significant reduction in hematological values (red blood cells (p<0.0001), platelets (p=0.0005), total leukocytes (p=0.0002) and segmented neutrophils (p=0.0007) to this chemotherapeutic protocol. However, these were not sufficient to alter the degree of adverse effects caused by this type of treatment. These jointly assessed results indicate that the association between carboplatin and cyclophosphamide represents a feasible alternative for adjuvant treatment of female dogs with high grade mammary carcinomas and/or regional lymph node metastasis, as it contributes to the increase in survival rate (p=0,0044) of these female dogs, compared to carboplatin as a single chemotherapy treatment.