Evaluation of antitumor activity in a human breast tumor/nude mouse model with a special emphasis on treatment dose.
Eight lines of human breast tumors implanted in nude mice were treated with various antitumor agents at two different doses, maximum tolerated doses (MTD) and rational doses (RD) that were pharmacokinetically equivalent to the clinical doses; the response rates to both doses were compared. With MTD, the response rates to mitomycin C and vinblastine were 100%, and those to other agents including cyclophosphamide, nimustine (a water-soluble nitrosourea), vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 5-fluorouracil (5-FU), and methotrexate were 30%-50%, indicating high responsiveness to the former two agents. In contrast, when the RD were used, the response rates to the majority of these agents were 25%-40%, and those to vincristine and nimustine were 13% and 0%, respectively. These results agree with the reported clinical results compared with those with MTD, suggesting the importance of the use of clinically equivalent doses in the evaluation of antitumor efficacy in a human tumor/nude mouse system.
Inaba
M
M
Japanese Foundation for Cancer Research, Tokyo.
Kobayashi
T
T
Tashiro
T
T
Sakurai
Y
Y
Maruo
K
K
Ohnishi
Y
Y
Ueyama
Y
Y
Nomura
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin; D008937:Mitomycins / Q000493:pharmacokinetics / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D015376:Nimustine / Q000493:pharmacokinetics / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D008937:Mitomycins; D015376:Nimustine; D016685:Mitomycin; D014747:Vinblastine; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate