EFFICACY OF IFOSFAMIDE, DACARBAZINE, DOXORUBICIN AND CISPLATIN IN HUMAN SARCOMA XENOGRAFTS

The primary chemosensitivity of 16 highly malignant xenografted human soft-tissue sarcomas to ifosfamide, dacarbazine, adriamycin and cispla tin and the development of secondary drug resistance in two chemosensi tive sarcoma cell lines was tested in the xenograft system. Single-dos e single-agent treatments with 350 mg kg(-1) ifosfamide, 200 mg kg(-1) dacarbazine, 10 mg kg(-1) doxorubicin and 6.6 mg kg(-1) cisplatin wer e administered and response measured as specific growth delay. Since i fosfamide induced unexpectedly higher toxicity, response was corrected based on the shape of the dose-response curve for ifosfamide. Taking a specific growth delay > 3 as the cut-off point for chemosensitivity, ifosfamide, dacarbazine, doxorubicin and cisplatin were effective in 10/16, 4/16, 2/16 and 1/16 sarcoma cell lines respectively. Five out o f 16 sarcoma cell lines were resistant to all tested drugs. Ifosfamide -resistant sarcoma lines were also resistant to doxorubicin and cispla tin, indicating a high degree of cross-resistance. Dacarbazine was sti ll effective in 1/6 ifosfamide-resistant sarcoma cell lines. Secondary drug resistance developed slowly after doxorubicin and ifosfamide pre treatments at moderate selection pressure and developed rapidly after dacarbazine pretreatment at high selection pressure.