Abstract
The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented. The TDL regimen was safe and well tolerated. The incidence of side effects was comparable in both groups. Plasma cells have been cultured in vitro with thalidomide and lovastatin to assess the impact of both drugs on the apoptosis rate of plasma cells. In vitro experiments revealed that the combination of thalidomide and lovastatin induced higher apoptosis rate than apoptosis induced by each drug alone. Our results suggest that the addition of lovastatin to the TD regimen may improve the response rate in patients with relapsed or refractory myeloma.
Publication types
-
Multicenter Study
-
Randomized Controlled Trial
MeSH terms
-
Aged
-
Antineoplastic Agents, Hormonal / adverse effects
-
Antineoplastic Agents, Hormonal / therapeutic use
-
Antineoplastic Combined Chemotherapy Protocols / adverse effects
-
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
-
Dexamethasone / administration & dosage
-
Dexamethasone / adverse effects
-
Dexamethasone / therapeutic use
-
Drug Resistance, Neoplasm
-
Female
-
Humans
-
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
-
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
-
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
-
Immunomodulation*
-
Immunosuppressive Agents / administration & dosage
-
Immunosuppressive Agents / adverse effects
-
Immunosuppressive Agents / therapeutic use
-
Lovastatin / administration & dosage
-
Lovastatin / adverse effects
-
Lovastatin / therapeutic use*
-
Male
-
Middle Aged
-
Multiple Myeloma / drug therapy*
-
Multiple Myeloma / immunology
-
Multiple Myeloma / therapy
-
Neoplasm Recurrence, Local / drug therapy*
-
Neoplasm Recurrence, Local / immunology
-
Neoplasm Recurrence, Local / therapy
-
Salvage Therapy* / adverse effects
-
Stem Cell Transplantation*
-
Survival Analysis
-
Thalidomide / administration & dosage
-
Thalidomide / adverse effects
-
Thalidomide / therapeutic use
-
Transplantation, Autologous
Substances
-
Antineoplastic Agents, Hormonal
-
Hydroxymethylglutaryl-CoA Reductase Inhibitors
-
Immunosuppressive Agents
-
Thalidomide
-
Dexamethasone
-
Lovastatin