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 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.
Yamashita
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Department of Veterinary Surgery, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Japan.
Maruo
K
K
Suzuki
K
K
Shirota
K
K
Kobayashi
K
K
Hioki
K
K
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006651:Histocytochemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D018709:Statistics, Nonparametric; D014747:Vinblastine / Q000008:administration & dosage / Q000494:pharmacology; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil