PMID- 23364621
OWN - NLM
STAT- MEDLINE
DCOM- 20131021
LR  - 20220410
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 8
DP  - 2013 Aug
TI  - Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics 
      and safety.
PG  - 1707-14
LID - 10.1038/leu.2013.29 [doi]
AB  - This phase 2 study assessed the safety, pharmacokinetics, pharmacodynamics and 
      efficacy of carfilzomib, a selective proteasome inhibitor, in patients with 
      multiple myeloma and varying degrees of renal impairment, including patients on 
      chronic hemodialysis. Patients were grouped by creatinine clearance: >80 ml/min, 
      50-80 ml/min, 30-49 ml/min, <30 ml/min and chronic hemodialysis. Carfilzomib was 
      administered on days 1, 2, 8, 9, 15 and 16 in 28-day cycles: 15 mg/m(2) (Cycle 
      1), 20 mg/m(2) (Cycle 2) and 27 mg/m(2) (Cycles 3+). There were no differences in 
      carfilzomib clearance or exposure among patients with normal renal function and 
      any group with renal impairment. Grade 3/4 adverse events (AEs) included anemia 
      (28.0%), thrombocytopenia (20.0%), lymphopenia (18.0%) and fatigue (14.0%). AEs 
      were similar among groups. At 15 mg/m(2), proteasome inhibition up to 85% was 
      observed and did not differ among groups. Although nearly 50% of patients were 
      refractory to both bortezomib and lenalidomide, end of study partial response or 
      better (overall response rate) was 25.5% with 7.9 months median duration of 
      response. In conclusion, the pharmacokinetics and safety of carfilzomib were not 
      influenced by the degree of baseline renal impairment, including in patients on 
      dialysis, and carfilzomib was well tolerated and demonstrated promising efficacy.
FAU - Badros, A Z
AU  - Badros AZ
AD  - M and S Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA. 
      abadros@umm.edu
FAU - Vij, R
AU  - Vij R
FAU - Martin, T
AU  - Martin T
FAU - Zonder, J A
AU  - Zonder JA
FAU - Kunkel, L
AU  - Kunkel L
FAU - Wang, Z
AU  - Wang Z
FAU - Lee, S
AU  - Lee S
FAU - Wong, A F
AU  - Wong AF
FAU - Niesvizky, R
AU  - Niesvizky R
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130131
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Oligopeptides)
RN  - 0 (Proteasome Inhibitors)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Female
MH  - Humans
MH  - Kidney Function Tests
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*complications/*drug therapy
MH  - Oligopeptides/adverse effects/pharmacokinetics/*therapeutic use
MH  - Proteasome Inhibitors/adverse effects/pharmacokinetics/*therapeutic use
MH  - Renal Insufficiency/*complications
MH  - Treatment Outcome
PMC - PMC3740399
EDAT- 2013/02/01 06:00
MHDA- 2013/10/22 06:00
CRDT- 2013/02/01 06:00
PHST- 2012/10/18 00:00 [received]
PHST- 2013/01/15 00:00 [revised]
PHST- 2013/01/21 00:00 [accepted]
PHST- 2013/02/01 06:00 [entrez]
PHST- 2013/02/01 06:00 [pubmed]
PHST- 2013/10/22 06:00 [medline]
AID - leu201329 [pii]
AID - 10.1038/leu.2013.29 [doi]
PST - ppublish
SO  - Leukemia. 2013 Aug;27(8):1707-14. doi: 10.1038/leu.2013.29. Epub 2013 Jan 31.