Influência da ciclofosfamida na farmacocinética da carboplatina em cadelas com carcinomas mamários e graduação dos efeitos adversos decorrentes da quimioterapia

Abstract

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.