Experimental chemotherapy against canine mammary cancer xenograft in SCID mice and its prediction of clinical effect

The effectiveness of 6 antitumor agents has been evaluated for canine mamma ry gland tumor (CMG-6) serially transplanted into severe combined immunodef iciency (SCID) mice. CMG-6 diagnosed as a solid carcinoma was subcutaneousl y transplanted into SCID mice and six antitumor agents were intravenously g iven 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, dox orubicin (DXR) 6, cisplatin (CDDP) 5, vincristine (VCR) 1.6, vinblastine (V LB) 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 clinica l dose (AUCdog)/AUC of mice given a MED (AUCmouse) ratios from published re ferences. The AUC ratios were as follows; CPM 2.24, DXR 0.19, CDDP 1.20, VC R 0.04, VLB <1.24 and 5-FU 1.15. Drugs indicating more than 1.0 in AUCdog/A UCmouse ratio were CPM, CDDP and 5-FU, and would be suggested as effective in the original patient with CMG-6. The combination chemotherapy using clin ically equivalent doses in CDDP and CPM, which were the two highest values in AUCdog/AUCmouse ratio by single agent therapy, was performed and shown t o have additional effects as compared to the responsiveness of each agent a gainst CMG-6.