PMID- 23040437
OWN - NLM
STAT- MEDLINE
DCOM- 20130522
LR  - 20230202
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 12
IP  - 5
DP  - 2012 Oct
TI  - An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, 
      single-agent carfilzomib in patients with relapsed and refractory multiple 
      myeloma.
PG  - 310-8
LID - S2152-2650(12)00148-6 [pii]
LID - 10.1016/j.clml.2012.08.003 [doi]
AB  - An open-label single-arm multicenter pilot phase II study of the next-generation 
      selective proteasome inhibitor carfilzomib was conducted in 46 patients with 
      relapsed and refractory multiple myeloma (MM) after >/= 2 previous therapies. The 
      best overall response rate (ORR) was 16.7%, with a median duration of response of 
      7.2 months. This pilot study was the first phase II single-agent trial conducted 
      with carfilzomib. BACKGROUND: Carfilzomib is a next-generation selective 
      proteasome inhibitor that irreversibly binds its target and has demonstrated 
      single-agent activity in patients with bortezomib-resistant multiple myeloma 
      (MM). PX-171-003-A0, an open-label single-arm multicenter pilot phase II study, 
      enrolled 46 patients with relapsed MM after >/= 2 previous therapies including 
      bortezomib and an immunomodulator (thalidomide or lenalidomide) and disease 
      refractory to the last treatment regimen preceding study entry. METHODS: Patients 
      received carfilzomib 20 mg/m(2) intravenously on days 1, 2, 8, 9, 15, and 16 
      every 28 days for up to 12 cycles. Responses in 42 evaluable patients were 
      assessed per International Myeloma Working Group Uniform Response Criteria, with 
      minimal response assessed per European Group for Blood and Marrow Transplantation 
      (EBMT) criteria. RESULTS: The primary endpoint of best ORR was 16.7%, including 7 
      partial responses. Median duration of response was 7.2 months. Clinical benefit 
      response (CBR) rate was 23.8% with a median duration of response of 13.8 months. 
      The most common treatment-emergent adverse events (AEs) of any grade were anemia 
      (73.9%), fatigue (69.6%), and thrombocytopenia (50.0%). Notably, peripheral 
      neuropathy and neuropathy-related AEs were generally mild and infrequent. 
      CONCLUSION: This pilot study was the first phase II single-agent trial conducted 
      with carfilzomib. Based on these findings, the study was amended to test a higher 
      carfilzomib dose in an additional 250 patients (PX-171-003-A1).
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Jagannath, Sundar
AU  - Jagannath S
AD  - Mount Sinai Medical Center, New York, NY 10029, USA. sundar.jagannath@mssm.edu
FAU - Vij, Ravi
AU  - Vij R
FAU - Stewart, A Keith
AU  - Stewart AK
FAU - Trudel, Suzanne
AU  - Trudel S
FAU - Jakubowiak, Andrzej J
AU  - Jakubowiak AJ
FAU - Reiman, Tony
AU  - Reiman T
FAU - Somlo, George
AU  - Somlo G
FAU - Bahlis, Nizar
AU  - Bahlis N
FAU - Lonial, Sagar
AU  - Lonial S
FAU - Kunkel, Lori A
AU  - Kunkel LA
FAU - Wong, Alvin
AU  - Wong A
FAU - Orlowski, Robert Z
AU  - Orlowski RZ
FAU - Siegel, David S
AU  - Siegel DS
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Boronic Acids)
RN  - 0 (Oligopeptides)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Boronic Acids/pharmacology
MH  - Bortezomib
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Neoplasm
MH  - Drug Tolerance
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Oligopeptides/*administration & dosage/adverse effects
MH  - Pilot Projects
MH  - Proteasome Inhibitors/*administration & dosage/adverse effects
MH  - Pyrazines/pharmacology
MH  - *Secondary Prevention
EDAT- 2012/10/09 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/10/09 06:00
PHST- 2012/06/08 00:00 [received]
PHST- 2012/07/18 00:00 [revised]
PHST- 2012/08/21 00:00 [accepted]
PHST- 2012/10/09 06:00 [entrez]
PHST- 2012/10/09 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - S2152-2650(12)00148-6 [pii]
AID - 10.1016/j.clml.2012.08.003 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):310-8. doi: 
      10.1016/j.clml.2012.08.003.