VAD-CYCLOSPORINE THERAPY FOR VAD-RESISTANT MULTIPLE-MYELOMA

Few effective treatments are available for patients with multiple myel oma that is resistant to vincristine-doxorubicin by continuous infusio n with high dose dexamethasone (VAD). In order to modulate p-glycoprot ein, the multidrug resistance gene product, we administered a VAD-cycl osporine combination to patients with confirmed resistance to VAD. Twe nty-five patients with multiple myeloma resistant to VAD received cycl osporine 4 mg/kg infused over 2 hours followed by a continuous infusio n of 10 mg/kg/24 hrs for a total of 108 hours. VAD was given concurren tly as a continuous infusion of vincristine 0.3 mg and doxorubicin 9 m g/m(2) daily for 4 days with oral dexamethasone 20 mg/m(2)/day for 4 d ays beginning on days 1, 9 and 17. Clinical response and toxicity were correlated with MDR expression in plasma cells and the effects of cyc losporine on liver function. Six of 25 patients responded (24%; 95% CI 9-45%) with a median remission time of 7 months. Clinical response di d not correlate with either the measured or the calculated MDR express ion in plasma cells. Responses occurred more frequently in patients wh o developed high cyclosporine blood levels and paralytic ileus. The oc casional benefit from VAD-cyclosporine for resistant multiple myeloma appeared to be due to a higher bioeffective dose of VAD rather than su ccessful modulation of MDR.