Experimental Chemotherapy against Canine Mammary Cancer Xenograft in SCID Mice and Its Prediction of Clinical Effect

Abstract

The effectiveness of 6 antitumor agents has been evaluated for canine mammary gland tumor (CMG-6) serially transplanted into severe combined immunodeficiency (SCID) mice. CMG-6 diagnosed as a solid carcinoma was subcutaneously transplanted into SCID mice and six antitumor agents were intravenously given to the mice as a single injection. The effectiveness was evaluated by Treatment group/Control group percent (T/C %) and statistical significance determined by Mann-Whitney's U-test in tumor volume. The minimum effective doses (MEDs: mg/kg) of mice were as follows; cyclophosphamide (CPM) 65, doxorubicin (DXR) 6, cisplatin (CDDP) 5, vincristine (VCR) 1.6, vinblastine (VLB) more than 5.5, 5-fluorouracil (5-FU) 105. Clinical effects of the drugs were predicted based on area under the curve (AUC) of dogs given a clinical dose (AUCdog)/AUC of mice given a MED (AUCmouse) ratios from published references. The AUC ratios were as follows; CPM 2.24, DXR 0.19, CDDP 1.20, VCR 0.04, VLB < 1.24 and 5-FU 1.15. Drugs indicating more than 1.0 in AUCdog/AUCmouse ratio were CPM, CDDP and 5-FU, and would be suggested as effective in the original patient with CMG-6. The combination chemotherapy using clinically equivalent doses in CDDP and CPM, which were the two highest values in AUCdog/AUCmouse ratio by single agent therapy, was performed and shown to have additional effects as compared to the responsiveness of each agent against CMG-6.