BACKGROUND: Multiple myeloma is considered to be a drug responsive disease; however, there is no cure for this disease and virtually all patients will develop drug resistance. One form of drug resistance that has been documented is the multidrug resistance phenotype or MDR. METHODS: A randomized trial of the combination of vincristine, doxorubicin, and dexamethasone (VAD) and VAD plus oral verapamil (VAD/v) in drug refractory multiple myeloma patients was performed by the Southwestern Oncology Group. Verapamil was used as a chemosensitizing agent to attempt to overcome or prevent MDR and improve the therapeutic outcome. RESULTS: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 median survival of 10 months for the VAD arm and 13 months for the VAD/v arm. The toxicity profile was also similar for both treatments, with myelosuppression being the dose-limiting toxicity. No significant correlation was observed between expression of P-glycoprotein, serum verapamil levels, and response to therapy. CONCLUSIONS: No beneficial effect was observed from the addition of oral verapamil to the VAD chemotherapy regimen for the treatment of drug-resistant myeloma patients. More effective and less toxic chemosensitizers are needed to study the role of chemosensitizers in reversing MDR in the clinic.
RCT Entities:
BACKGROUND:Multiple myeloma is considered to be a drug responsive disease; however, there is no cure for this disease and virtually all patients will develop drug resistance. One form of drug resistance that has been documented is the multidrug resistance phenotype or MDR. METHODS: A randomized trial of the combination of vincristine, doxorubicin, and dexamethasone (VAD) and VAD plus oralverapamil (VAD/v) in drug refractory multiple myelomapatients was performed by the Southwestern Oncology Group. Verapamil was used as a chemosensitizing agent to attempt to overcome or prevent MDR and improve the therapeutic outcome. RESULTS: 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 median survival of 10 months for the VAD arm and 13 months for the VAD/v arm. The toxicity profile was also similar for both treatments, with myelosuppression being the dose-limiting toxicity. No significant correlation was observed between expression of P-glycoprotein, serum verapamil levels, and response to therapy. CONCLUSIONS: No beneficial effect was observed from the addition of oral verapamil to the VAD chemotherapy regimen for the treatment of drug-resistant myelomapatients. More effective and less toxic chemosensitizers are needed to study the role of chemosensitizers in reversing MDR in the clinic.
Authors: Edith J Mensah-Osman; Dafydd G Thomas; Michelle M Tabb; Jose M Larios; Dennis P Hughes; Thomas J Giordano; Michelle L Lizyness; James M Rae; Bruce Blumberg; Paul F Hollenberg; Laurence H Baker Journal: Cancer Date: 2007-03-01 Impact factor: 6.860
Authors: U Mayer; E Wagenaar; J H Beijnen; J W Smit; D K Meijer; J van Asperen; P Borst; A H Schinkel Journal: Br J Pharmacol Date: 1996-11 Impact factor: 8.739
Authors: Robert O'Connor; Melissa G Ooi; Justine Meiller; Jana Jakubikova; Steffen Klippel; Jake Delmore; Paul Richardson; Kenneth Anderson; Martin Clynes; Constantine S Mitsiades; Peter O'Gorman Journal: Cancer Chemother Pharmacol Date: 2013-04-16 Impact factor: 3.333
Authors: Erica Lynn Bradshaw-Pierce; Todd M Pitts; Aik-Choon Tan; Kelly McPhillips; Mark West; Daniel L Gustafson; Charles Halsey; Leslie Nguyen; Nathan V Lee; Julie L C Kan; Brion William Murray; S Gail Eckhardt Journal: Front Pharmacol Date: 2013-03-22 Impact factor: 5.810