Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening.

We have used three continuous human neuroblastoma cell lines to establish patterns of in vitro drug sensitivities, as judged by clonogenic assay. We evaluated 12 'standard' antitumor drugs already in clinical usage, and tested four newer analogues, one of cisplatin and three of doxorubicin, and the investigational agent desferrioxamine. A certain heterogeneity of drug sensitivities was noted amongst these three cell lines, but a few general conclusions can be drawn. Responses of all lines tested were similar for actinomycin D, dibromodulcitol, doxorubicin, 5-fluorouracil, melphalan and VM 26. However, line CHP 100 proved hypersensitive to amsacrine, bleomycin, methotrexate and vincristine yet refractory to cisplatin, carboplatin and VP-16, compared with the other two lines. This emphasizes the necessity for using a panel of cell lines for this type of drug screening programme. A comparison of IC50 drug concentrations, derived from these in vitro tests, with plasma levels achievable clinically, indicate that VP-16, VM 26, doxorubicin and cisplatin appear to be the most effective agents in this tumor type. This finding is consistent with clinical experience. The newer doxorubicin analogues proved 2-5 fold more cytotoxic than doxorubicin itself. However, these differences also appear to be reflected in the lower dose ranges now being tested in phase I/II clinical trials. Desferrioxamine, which proved cytotoxic against all three neuroblastoma cell lines, exerted comparable cytotoxicity against two of the three non-neuroblastoma human tumor cell lines evaluated. Therefore we suggest that attempts to identify any specific antineuroblastoma activities by new investigational agents using this type of model systems require evaluation against panels of both neuroblastoma and non-neuroblastoma lines.