title: First clinical experience with simvastatin to overcome drug resistance in refractory multiple myeloma.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Medizinische Klinik Innenstadt - Klinikum der Universität München, Munich, Germany. ralf.schmidmaier@med.uni-muenchen.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Schmidmaier
authors.forename: Philipp
authors.initials: P
authors.lastname: Baumann
authors.forename: Irmgard
authors.initials: I
authors.lastname: Bumeder
authors.forename: Gerold
authors.initials: G
authors.lastname: Meinhardt
authors.forename: Christian
authors.initials: C
authors.lastname: Straka
authors.forename: Bertold
authors.initials: B
authors.lastname: Emmerich
mesh_terms: 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
chemical_list: D001897:Boronic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009588:Nitrogen Mustard Compounds; D011719:Pyrazines; D000069286:Bortezomib; D000069461:Bendamustine Hydrochloride; D019821:Simvastatin