A PHASE-III RANDOMIZED STUDY OF ORAL VERAPAMIL AS A CHEMOSENSITIZER TO REVERSE DRUG-RESISTANCE IN PATIENTS WITH REFRACTORY MYELOMA - A SOUTHWEST-ONCOLOGY-GROUP STUDY

Background. Multiple myeloma is considered to be a drug responsive dis ease; however, there is no cure for this disease and virtually all pat ients will develop drug resistance. One form of drug resistance that h as been documented is the multidrug resistance phenotype or MDR. Metho ds. A randomized trial of the combination of vincristine, doxorubicin, and dexamethasone (VAD) and VAD plus oral verapamil (VAD/v) in drug r efractory multiple myeloma patients was performed by the Southwestern Oncology Group. Verapamil was used as a chemosensitizing agent to atte mpt to overcome of prevent MDR and improve the therapeutic outcome. Re sults. Response rates between the two treatment arms were similar with an overall response rate of 41% for the VAD alone arm and 36% for the VAD/v arm. Overall survival of patients was also similar with a media n survival of 10 months for the VAD arm and 13 months for the VAD/v ar m. The toxicity profile was also similar for both treatments, with mye losuppression being the dose-limiting toxicity. No significant correla tion was observed between expression of P-glycoprotein, serum verapami l levels, and response to therapy. Conclusions. No beneficial effect w as observed from the addition of oral verapamil to the VAD chemotherap y regimen for the treatment of drug-resistant myeloma patients. More e ffective and less toxic chemosensitizers are needed to study the role of chemosensitizers in reversing MDR in the clinic.