EVALUATION OF RESISTANCE INDEX OF SEVERAL ANTICANCER AGENTS ON PARENTAL AND RESISTANT P-388 CELL-LINES

Multidrug resistance is frequently detected in haematological malignan cies and in acute leukaemias with a poor prognosis. In the last few ye ars, several reports seem to suggest that the new anthracycline deriva tive idarubicin and the anthraquinone mitoxantrone have some advantage s in the management of untreated or relapsed acute leukaemias compared with older anthracyclines. This could be due to a different interacti on of these drugs with multidrug resistance. To evaluate this possibil ity, we compared the activity of doxorubicin (DOXO), epirubicin (EPI), idarubicin (IDA) and mitoxantrone (MITO) on a murine, multidrug resis tant, leukaemic cell line (P-388/Dx) cultured in vitro. ID50 of IDA an d MITO was in the ng range whereas that of DOXO and EPI was in the mu g range. Moreover, IDA has a resistance index of 50 whereas DOXO has o ne of 250. Verapamil is able to almost completely abolish the resistan ce to IDA. Efflux experiments confirm that verapamil increases IDA int racellular concentration. IDA and MITO appear to be less involved in m ultidrug resistance than older anthracyclines.