PMID- 25557740
OWN - NLM
STAT- MEDLINE
DCOM- 20150601
LR  - 20151119
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 90
IP  - 4
DP  - 2015 Apr
TI  - Effect of cumulative bortezomib dose on survival in multiple myeloma patients 
      receiving bortezomib-melphalan-prednisone in the phase III VISTA study.
PG  - 314-9
LID - 10.1002/ajh.23933 [doi]
AB  - This analysis, using data from the bortezomib-melphalan-prednisone (VMP) arm of 
      the Phase III VISTA study, investigated whether increased cumulative bortezomib 
      dose could improve overall survival (OS) in transplant-ineligible patients with 
      previously untreated multiple myeloma. Median cumulative bortezomib dose received 
      by the 340 patients was 39 mg/m(2); this was selected as the cut-off for defining 
      the dose groups to be compared for OS. Patient characteristics were well balanced 
      between dose groups except for age. OS was significantly longer in the higher 
      (>/=39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib dose group (median 
      66.3 vs. 46.2 months; hazard ratio (HR) 0.533, P < 0.0001; age-adjusted HR 0.561, 
      P = 0.0002). To overcome confounding effects of early discontinuations/deaths, 
      which were more common in the lower cumulative dose group (27 vs. 4% of patients 
      discontinued due to adverse events (AEs) in the lower and higher cumulative dose 
      groups, respectively), a landmark analysis was conducted at 180 days, eliminating 
      patients who died or discontinued before this time from the analysis. OS from 
      this landmark remained significantly longer in the higher dose group (median 60.4 
      vs. 50.3 months; HR 0.709, P = 0.0372). Thus, higher cumulative bortezomib dose, 
      reflecting prolonged treatment duration and/or dose intensity, appears associated 
      with improved OS. Approaches to achieve higher cumulative doses could include 
      subcutaneous bortezomib administration, dose/schedule modifications, continuing 
      therapy in responding patients, and proactive AE management.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Mateos, Maria Victoria
AU  - Mateos MV
AD  - Hospital Universitario Salamanca, Instituto Biosanitario De Salamanca (IBSAL), 
      Spain.
FAU - Richardson, Paul G
AU  - Richardson PG
FAU - Dimopoulos, Meletios A
AU  - Dimopoulos MA
FAU - Palumbo, Antonio
AU  - Palumbo A
FAU - Anderson, Kenneth C
AU  - Anderson KC
FAU - Shi, Hongliang
AU  - Shi H
FAU - Elliott, Jennifer
AU  - Elliott J
FAU - Dow, Edward
AU  - Dow E
FAU - van de Velde, Helgi
AU  - van de Velde H
FAU - Niculescu, Liviu
AU  - Niculescu L
FAU - San Miguel, Jesus F
AU  - San Miguel JF
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150227
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - Q41OR9510P (Melphalan)
RN  - VB0R961HZT (Prednisone)
SB  - IM
CIN - Am J Hematol. 2015 Aug;90(8):E146. PMID: 25916914
CIN - Am J Hematol. 2015 Aug;90(8):E146. PMID: 26043930
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/*therapeutic use
MH  - Boronic Acids/*administration & dosage/adverse effects/*therapeutic use
MH  - Bortezomib
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Melphalan/administration & dosage/adverse effects/therapeutic use
MH  - Multiple Myeloma/*drug therapy/*mortality
MH  - Prednisone/administration & dosage/adverse effects/therapeutic use
MH  - Pyrazines/*administration & dosage/adverse effects/*therapeutic use
MH  - Survival Analysis
EDAT- 2015/01/06 06:00
MHDA- 2015/06/02 06:00
CRDT- 2015/01/06 06:00
PHST- 2014/09/15 00:00 [received]
PHST- 2014/12/03 00:00 [revised]
PHST- 2014/12/24 00:00 [accepted]
PHST- 2015/01/06 06:00 [entrez]
PHST- 2015/01/06 06:00 [pubmed]
PHST- 2015/06/02 06:00 [medline]
AID - 10.1002/ajh.23933 [doi]
PST - ppublish
SO  - Am J Hematol. 2015 Apr;90(4):314-9. doi: 10.1002/ajh.23933. Epub 2015 Feb 27.