Are there alternative strategies to overcoming multidrug resistance in AML?
An alternative strategy to circumvent pgp-mediated drug resistance is to use a combination of drugs that are not effluxed by this pathway: such drugs include AraC and idarubicin. The combination of fludarabine, AraC (FLAG)Idarubicin has been widely used in resistant or relapsed AML although studies as first-line treatment are rare. We have previously observed a high CR rate in response to FLAG in pgp-positive AML cases with primary resistance to DAT.37 Furthermore, when using a flow cytometric assay of cell survival, we observed that in vitro responses to FLAG differed from DAT, depending upon pgp status. Pgp-positive AML blasts were more sensitive to the combination of fludarabine/AraC than to daunorubicin/AraC. Conversely, pgp-negative blasts were more sensitive to daunorubicin/AraC.38 The efficacy of FLAG plus idarubicin compared to DA is being studied in the current MRC AML15 trial, which includes measurements of multidrug resistance proteins. This trial also incorporates the use o
