Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma

This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin’s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 =...

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Published in:Animals (Basel) 2022-11, Vol.12 (22), p.3109
Main Authors: Machado, Marília Carneiro, Yamamoto, Priscila Akemi, Pippa, Leandro Francisco, de Moraes, Natália Valadares, Neves, Fabiane Maria Fernandes, Portela, Ricardo Dias, Barrouin-Melo, Stella Maria, Hielm-Björkman, Anna, Godoy, Ana Leonor Pardo Campos, Estrela-Lima, Alessandra
Format: Article
Language:English
Subjects:
Animals
Blood tests
breast cancer
Cancer therapies
Carboplatin
Carcinoma
Cell division
Chemotherapy
Cyclophosphamide
dog
Dogs
Drug dosages
Erythrocytes
Evaluation
Intravenous administration
Leukocytes (neutrophilic)
Mammary gland
Mastectomy
Metastasis
metronomic chemotherapy
pharmacokinetic parameters
Pharmacokinetics
Pharmacology
Plasma
Quality control
Survival
survival rate
Tumors
Variability
Veterinary medicine
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Summary:This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin’s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or 300 mg/m2 i.v. carboplatin which was associated with 12.5 mg/m2 oral cyclophosphamide in a metronomic regimen (G2 = 8). The investigated animals underwent a clinical evaluation, a mastectomy, a carboplatin chemotherapy, and serial blood sampling for the pharmacokinetic analysis. The adverse events and survival rates were monitored. A non-compartmental analysis was applied to calculate the pharmacokinetic parameters of carboplatin in the 2nd and 4th chemotherapy cycles. Carboplatin PK showed high interindividual variability with a 10-fold variation in the area under the plasma concentration−time curve (AUC) in G1. The systemic plasma exposure to carboplatin was equivalent in both of the treatments considering the AUC and maximum plasma concentration (Cmax) values. Although the red blood cells (p < 0.0001), platelets (p = 0.0005), total leukocytes (p = 0.0002), and segmented neutrophils (p = 0.0007) were reduced in G2, the survival rate increased (p = 0.0044) when it was compared to G1. In conclusion, adding low daily doses of cyclophosphamide to a carboplatin therapy showed promising outcomes in female dogs with mammary tumors.
ISSN:2076-2615
2076-2615
DOI:10.3390/ani12223109