title: Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma.
abstract: OBJECTIVE
  Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety.
  
  
  METHODS
  Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m(2), thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m(2) for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ:λ free light chain ratio, CR, and nCR).
  
  
  RESULTS
  Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference post-transplantation versus baseline.
  
  
  CONCLUSIONS
  Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.
authors.affiliation: Wilhelminenspital, Vienna, Austria. heinz.ludwig@wienkav.at
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Luisa
authors.initials: L
authors.lastname: Viterbo
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.forename: Graca
authors.initials: G
authors.lastname: Esteves
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Stoppa
authors.forename: Don
authors.initials: D
authors.lastname: Robinson
authors.forename: Deborah
authors.initials: D
authors.lastname: Ricci
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Christopher
authors.initials: C
authors.lastname: Enny
authors.forename: Huaibao
authors.initials: H
authors.lastname: Feng
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D020360:Neoadjuvant Therapy; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide