PMID- 23091109
OWN - NLM
STAT- MEDLINE
DCOM- 20130514
LR  - 20220309
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 31
IP  - 2
DP  - 2013 Jan 10
TI  - Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or 
      without cyclophosphamide as induction therapy in previously untreated multiple 
      myeloma.
PG  - 247-55
LID - 10.1200/JCO.2011.39.5137 [doi]
AB  - PURPOSE: 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. PATIENTS AND 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 kappa:lambda 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. CONCLUSION: 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.
FAU - Ludwig, Heinz
AU  - Ludwig H
AD  - Wilhelminenspital, Vienna, Austria. heinz.ludwig@wienkav.at
FAU - Viterbo, Luisa
AU  - Viterbo L
FAU - Greil, Richard
AU  - Greil R
FAU - Masszi, Tamas
AU  - Masszi T
FAU - Spicka, Ivan
AU  - Spicka I
FAU - Shpilberg, Ofer
AU  - Shpilberg O
FAU - Hajek, Roman
AU  - Hajek R
FAU - Dmoszynska, Anna
AU  - Dmoszynska A
FAU - Paiva, Bruno
AU  - Paiva B
FAU - Vidriales, Maria-Belen
AU  - Vidriales MB
FAU - Esteves, Graca
AU  - Esteves G
FAU - Stoppa, Anne Marie
AU  - Stoppa AM
FAU - Robinson, Don Jr
AU  - Robinson D Jr
FAU - Ricci, Deborah
AU  - Ricci D
FAU - Cakana, Andrew
AU  - Cakana A
FAU - Enny, Christopher
AU  - Enny C
FAU - Feng, Huaibao
AU  - Feng H
FAU - van de Velde, Helgi
AU  - van de Velde H
FAU - Harousseau, Jean-Luc
AU  - Harousseau JL
LA  - eng
SI  - ClinicalTrials.gov/NCT00531453
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121022
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Boronic Acids/administration & dosage/adverse effects
MH  - Bortezomib
MH  - Cyclophosphamide/administration & dosage/adverse effects
MH  - Dexamethasone/administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Induction Chemotherapy
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/surgery
MH  - Neoadjuvant Therapy
MH  - Pyrazines/administration & dosage/adverse effects
MH  - Risk Assessment
MH  - Thalidomide/administration & dosage/adverse effects
EDAT- 2012/10/24 06:00
MHDA- 2013/05/15 06:00
CRDT- 2012/10/24 06:00
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
AID - JCO.2011.39.5137 [pii]
AID - 10.1200/JCO.2011.39.5137 [doi]
PST - ppublish
SO  - J Clin Oncol. 2013 Jan 10;31(2):247-55. doi: 10.1200/JCO.2011.39.5137. Epub 2012 
      Oct 22.