Assessment of metronomic chemotherapy-induced DNA damage in peripheral blood leukocytes from canine mammary cancer patients using the alkaline comet assay

Mammary cancer is a disease that requires effective treatments. Conventional chemotherapy, while effective, often causes harmful side effects. In contrast, metronomic chemotherapy (mCHT), which involves the continuous administration of low doses of anticancer drugs, is presented as a less aggressive alternative. In this study, the genotoxic impact of treatment with Cyclophosphamide and Meloxicam under the mCHT approach was evaluated in ten canine (Canis lupus familiaris) patients with mammary carcinoma after undergoing mastectomy. The patients underwent monthly evaluations, including chest X-rays, blood tests, and the alkaline comet assay to measure genotoxic effects of the antineoplastic drugs. These results were compared with those of a group that received conventional chemotherapy. The results revealed that patients treated with mCHT experienced significantly lower levels of DNA damage compared to those who received conventional chemotherapy. Furthermore, DNA damage decreased over time during mCHT, suggesting that dogs may have developed tolerance to the treatment. Blood parameters remained stable in the mCHT-treated group, and X-rays showed no signs of recurrence or metastasis. All dogs survived during the one- year follow-up without mammary cancer recurrence. It is concluded that mCHT with Cyclophosphamide appears to be a less aggressive therapeutic option with a more favorable genotoxic profile in the treatment of mammary cancer in dogs.