ANTIPROLIFERATIVE POTENTIAL OF CYTOSTATIC DRUGS ON NEUROBLASTOMA-CELLS IN-VITRO

The role of single drugs in the treatment of neuroblastoma is poorly d efined. We, therefore, tested neuroblastoma cell survival after a 72 h exposure to one of 19 cytostatic drugs by monolayer proliferation ass ay. 6 cell lines (IMR-5, Kelly, SK-N-SH, GI-CA-N, CHP-100, CHP-134) we re selected on the basis of MYCN amplification and PGY1 overexpression . ED(50) drug concentrations were related to plasma levels achievable in patients during chemotherapy. More effective substances were mitoxa ntrone, doxorubicin, hydroxyurea, bleomycin, dactinomycin, cisplatinum , thiotepa, melphalan, carboplatinum, etoposide, vincristine, cytarabi ne, 6-thioguanine, cyclophosphamide, ifosfamide and zilascorb. Parenta l drugs (cyclophosphamide, cisplatinum) appeared more cytotoxic on a m olar basis than derived drugs (ifosfamide, carboplatinum). Less effect ive drugs included 5-fluorouracil, 6-mercaptopurine, CCNU and procarba zine. Fractional application of a given dose was more efficient than a single dose of cyclophosphamide, ifosfamide and cisplatinum. The test ed neuroblastoma cell lines showed distinct sensitivities to cytostati c drugs. Cell lines with MYCN amplification appeared more sensitive th an PGY1 overexpressing cells. In conclusion, comparative in vitro test ing of cytostatic drugs may provide a rationale for their clinical eva luation. Investigation of drug combinations and application of the mon olayer proliferation assay to tumour biopsy material for preclinical c hemosensitivity testing are clearly warranted.