PMID- 18200040
OWN - NLM
STAT- MEDLINE
DCOM- 20080604
LR  - 20151119
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 22
IP  - 4
DP  - 2008 Apr
TI  - Efficacy and safety of bortezomib in patients with renal impairment: results from 
      the APEX phase 3 study.
PG  - 842-9
LID - 10.1038/sj.leu.2405087 [doi]
AB  - Renal impairment is associated with poor prognosis in multiple myeloma (MM). This 
      subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for 
      Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone 
      assessed efficacy and safety in patients with relapsed MM with varying degrees of 
      renal impairment (creatinine clearance (CrCl) <30, 30-50, 51-80 and >80 ml 
      min(-1)). Time to progression (TTP), overall survival (OS) and safety were 
      compared between subgroups with CrCl < or =50 ml min(-1) (severe-to-moderate) and 
      >50 ml min(-1) (no/mild impairment). Response rates with bortezomib were similar 
      (36-47%) and time to response rapid (0.7-1.6 months) across subgroups. Although 
      the trend was toward shorter TTP/OS in bortezomib patients with 
      severe-to-moderate vs no/mild impairment, differences were not significant. OS 
      was significantly shorter in dexamethasone patients with CrCl < or =50 vs >50 ml 
      min(-1) (P=0.003), indicating that bortezomib is more effective than 
      dexamethasone in overcoming the detrimental effect of renal impairment. Safety 
      profile of bortezomib was comparable between subgroups. With dexamethasone, grade 
      3/4 adverse events (AEs), serious AEs and discontinuations for AEs were 
      significantly elevated in patients with CrCl < or =50 vs >50 ml min(-1). These 
      results indicate that bortezomib is active and well tolerated in patients with 
      relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not 
      substantially affected by severe-to-moderate vs no/mild impairment.
FAU - San-Miguel, J F
AU  - San-Miguel JF
AD  - Department of Hematology, Hospital Universitario. CIC Universidad de 
      Salamanca-CSIC, Salamanca, Spain. sanmigiz@usal.es
FAU - Richardson, P G
AU  - Richardson PG
FAU - Sonneveld, P
AU  - Sonneveld P
FAU - Schuster, M W
AU  - Schuster MW
FAU - Irwin, D
AU  - Irwin D
FAU - Stadtmauer, E A
AU  - Stadtmauer EA
FAU - Facon, T
AU  - Facon T
FAU - Harousseau, J-L
AU  - Harousseau JL
FAU - Ben-Yehuda, D
AU  - Ben-Yehuda D
FAU - Lonial, S
AU  - Lonial S
FAU - Goldschmidt, H
AU  - Goldschmidt H
FAU - Reece, D
AU  - Reece D
FAU - Blade, J
AU  - Blade J
FAU - Boccadoro, M
AU  - Boccadoro M
FAU - Cavenagh, J D
AU  - Cavenagh JD
FAU - Neuwirth, R
AU  - Neuwirth R
FAU - Boral, A L
AU  - Boral AL
FAU - Esseltine, D-L
AU  - Esseltine DL
FAU - Anderson, K C
AU  - Anderson KC
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080117
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/toxicity
MH  - Boronic Acids/*administration & dosage/toxicity
MH  - Bortezomib
MH  - Dexamethasone/administration & dosage/toxicity
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*complications/*drug therapy/mortality
MH  - Pyrazines/*administration & dosage/toxicity
MH  - Renal Insufficiency/*mortality/pathology
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 2008/01/18 09:00
MHDA- 2008/06/05 09:00
CRDT- 2008/01/18 09:00
PHST- 2008/01/18 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2008/01/18 09:00 [entrez]
AID - 2405087 [pii]
AID - 10.1038/sj.leu.2405087 [doi]
PST - ppublish
SO  - Leukemia. 2008 Apr;22(4):842-9. doi: 10.1038/sj.leu.2405087. Epub 2008 Jan 17.