Preclinical results of gemcitabinebased regimens for preoperative chemotherapy of spontaneous feline breast cancer

Abstract

Comparative preclinical study of chemotherapy regimen doxorubicin (DOX) + gemcitabine (GEM) for preoperative chemotherapy of spontaneous feline breast cancer and standard monochemotherapy with DOX alone was performed on transplantable murine mammary adenocarcinoma Ca55 in BDF1 hybrid mice model. The total GEM doses of 100 and 200 mg/kg for the triple course in combination with the single injection of 7.5 mg/kg of DOX were chosen to treat the established Ca755 tumor of 595.5 mm 3 average volume (preoperative treatment modeling). The combined chemotherapy showed an advantage of DOX + GEM regimen with GEM course dose of 200 mg/kg (70, 70 and 60 mg/kg, accordingly) as compared to other groups in terms of Tumor Growth Inhibition (TGI max=100% versus 96%; number of complete remissions (CR) 30% versus 0%, and enhanced Life Expectancy (LE) 163% versus 84-85%). The most effective regimen demonstrated dose-dependent therapeutic pathomorphism of grade II-III with 1.5-fold decrease of cell polymorphism and increase of cell differentiation. At the same time, the number of cells in mitosis decreased in 3-4 times and the number of apoptotic cells increased in 5-10 times. The results suggest that DOX + GEM combination with the unchanged components doses ratio has good potential for preoperative chemotherapy of locally advanced feline breast cancer and may be recommended for clinical study of this disease.