First clinical experience with simvastatin to overcome drug resistance in refractory multiple myeloma.
In vitro statins overcome cell adhesion-mediated drug resistance at non-toxic concentrations that are achievable in humans by standard dose simvastatin. A pilot phase-II trial was initiated to determine feasibility and antimyeloma efficacy. In six myeloma patients refractory to two cycles of bortezomib or bendamustine simvastatin was concomitantly administered during further two cycles. The therapy was well tolerated without grade 3/4 toxicity. Intrapatient (cycles I/II vs. III/IV) and interpatient comparison (vs. ten patients without simvastatin) showed reduction of drug resistance by inhibition of HMG-CoA-reductase. In summary, this is the first phase II experience to study antimyeloma activity of statins in humans.
Schmidmaier
Ralf
R
Department of Hematology and Oncology, Medizinische Klinik Innenstadt - Klinikum der Universität München, Munich, Germany. ralf.schmidmaier@med.uni-muenchen.de
Baumann
Philipp
P
Bumeder
Irmgard
I
Meinhardt
Gerold
G
Straka
Christian
C
Emmerich
Bertold
B
D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002448:Cell Adhesion; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D016879:Salvage Therapy / Q000379:methods*; D019821:Simvastatin / Q000008:administration & dosage* / Q000633:toxicity
D001897:Boronic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009588:Nitrogen Mustard Compounds; D011719:Pyrazines; D000069286:Bortezomib; D000069461:Bendamustine Hydrochloride; D019821:Simvastatin