CROSS-RESISTANCE OF DRUG-RESISTANT MURINE P388-LEUKEMIAS TO TAXOL INVIVO

The antimicrotubule agent taxol (NSC 125973) has shown clinical antitumor activity against several classically refractory tumors. We developed a drug-resistance profile for taxol using ten drug-resistant P388 leukemias to identify potentially useful guides for patient selection for further clinical trials of taxol and possible non-cross-resistant drug combinations with taxol. Multidrug-resistant P388 leukemias exhibited either clear (leukemia resistant to amsacrine) or marginal cross-resistance (leukemias resistant to doxorubicin, actinomycin D, and mitoxantrone) to taxol. Leukemias resistant to vincristine (non-multidrug-resistant leukemia), camptothecin, melphalan, cisplatin, 1-beta-D-arabinofuranosylcytosine, and methotrexate were not cross-resistant to taxol. The data suggest that (1) it may be important to exclude or to monitor with extra care patients who have previously been treated with amsacrine, doxorubicin, actinomycin D, or mitoxantrone and (2) a combination of one of the non-cross-resistant drugs and taxol might exhibit therapeutic synergism.