Document Detail

Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients.
MedLine Citation:
PMID:  21477075     Owner:  NLM     Status:  MEDLINE    
The ubiquitin-proteasome pathway regulates bone formation through osteoblast differentiation. We analyzed variation alkaline phosphatase (ALP) during carfilzomib treatment. Data from 38 patients enrolled in the PX-171-003 and 29 patients in PX-171-004 studies, for patients with relapsed/refractory myeloma, were analyzed. All patients received 20 mg/m(2) of carfilzomib on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Sixty-seven patients from ALP data were evaluable. In PX-171-003, the ORR (>PR) was 18% and the clinical benefit response (CBR; >MR) was 26%, while in PX-171-004, the ORR was 35.5% overall and 57% in bortezomib-naive patients. ALP increment from baseline was statistically different in patients who achieved ≥ VGPR compared with all others on Days 1 (P = 0.0049) and 8 (P = 0.006) of Cycle 2. In patients achieving a VGPR or better, ALP increased more than 15 units per liter at Cycle 2 Day 1 over baseline. An ALP increase over the same period of time was seen in 26%, 13% and 11% of patients achieving PR, MR, and SD, respectively. This retrospective analysis of patients with relapsed or refractory myeloma treated with single-agent carfilzomib indicates that early elevation in ALP is associated with subsequent myeloma response.
Maurizio Zangari; Monette Aujay; Fenghuang Zhan; Kristina L Hetherington; Tamara Berno; Ravi Vij; Sundar Jagannath; David Siegel; A Keith Stewart; Luhua Wang; Robert Z Orlowski; Andrew Belch; Andrzej Jakubowiak; George Somlo; Suzanne Trudel; Nizar Bahlis; Sagar Lonial; Seema Singhal; Vishal Kukreti; Guido Tricot
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article    
Journal Detail:
Title:  European journal of haematology     Volume:  86     ISSN:  1600-0609     ISO Abbreviation:  Eur. J. Haematol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-18     Completed Date:  2011-08-09     Revised Date:  2014-07-07    
Medline Journal Info:
Nlm Unique ID:  8703985     Medline TA:  Eur J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  484-7     Citation Subset:  IM    
Copyright Information:
© 2011 John Wiley & Sons A/S.
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MeSH Terms
Alkaline Phosphatase / blood*
Antineoplastic Agents / therapeutic use*
Boronic Acids / therapeutic use
Drug Resistance, Neoplasm
Middle Aged
Multiple Myeloma / drug therapy*,  enzymology*
Oligopeptides / therapeutic use*
Osteogenesis / drug effects
Protease Inhibitors / therapeutic use
Proteasome Inhibitors
Pyrazines / therapeutic use
Retrospective Studies
Treatment Outcome
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Boronic Acids; 0/Oligopeptides; 0/Protease Inhibitors; 0/Proteasome Inhibitors; 0/Pyrazines; 0/bortezomib; 0/carfilzomib; EC Phosphatase

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