Preclinical phase II studies in human tumor xenografts: A European multicenter follow-up study

摘要: Summary Background The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of human tumor xenografts predict phase II clinical activity. A first study confirmed efficacy doxorubicin and inactivity amsacrine against (Boven et al., Cancer Res: 52, 5940, 1992). In follow-up reported here, activities cisplatin, AZQ (diaziquone), pazelliptine retelliptine have been evaluated panel 40 established lines grown subcutaneously in nude mice. Design used represent carcinomas breast, colon, head + neck, ovary, small cell lung cancer (SCLC), non-small (NSCLC) melanoma. Drugs were administered intravenously on days 0 7. Doses for cisplatin 5 mg/kg, 3–7 20–80 mg/kg 6–12.5 selected give median loss about 10%–15% body weight. Results When activity was defined as specific growth delay > 1 inhibition 50%, then demonstrated 15 tested (3 6 2 NSCLC, 4 7 SCLC, melanoma ovarian cancers); active 23 38 (2 3 melanoma, (1 breast cancers, melanoma) while 39 (a xenograft) tested. Conclusions These results are reasonably consistent with but overpredict AZQ. Since investigational compounds, studies will provide prospective test this model. present previous one indicate that xenograft model could be suitable predicting novel compounds developed treatment patients.