PMID- 25666409
OWN - NLM
STAT- MEDLINE
DCOM- 20160119
LR  - 20220801
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 33
IP  - 2
DP  - 2015 Apr
TI  - Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of 
      life study of pegylated recombinant human arginase 1 in patients with advanced 
      hepatocellular carcinoma.
PG  - 496-504
LID - 10.1007/s10637-014-0200-8 [doi]
AB  - This study was designed to evaluate the efficacy, safety profile, 
      pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant 
      human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma 
      (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour 
      response was assessed every 8 weeks using RECIST 1.1 and modified RECIST 
      criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable 
      for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median 
      age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 
      15 patients achieving stable disease for >8 weeks. The median progression-free 
      survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival 
      (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was 
      significantly prolonged in patients with adequate arginine depletion (ADD) >2 
      months versus those who had </=2 months of ADD (6.4 versus 1.7 months; p = 0.01). 
      The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. 
      Transient liver dysfunctions (25%) were the most commonly reported serious AEs 
      and likely due to disease progression. Pharmacokinetic and pharmacodynamic data 
      showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The 
      overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 
      is well tolerated with a good toxicity profile in patients with advanced HCC. A 
      weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS 
      times were recorded for patients who had ADD for >2 months.
FAU - Yau, Thomas
AU  - Yau T
AD  - Department of Medicine, The University of Hong Kong, Hong Kong, China, 
      the@netvigator.com.
FAU - Cheng, Paul N
AU  - Cheng PN
FAU - Chan, Pierre
AU  - Chan P
FAU - Chen, Li
AU  - Chen L
FAU - Yuen, Jimmy
AU  - Yuen J
FAU - Pang, Roberta
AU  - Pang R
FAU - Fan, Sheung Tat
AU  - Fan ST
FAU - Wheatley, Denys N
AU  - Wheatley DN
FAU - Poon, Ronnie T
AU  - Poon RT
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150210
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 3.5.3.1 (ARG1 protein, human)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Area Under Curve
MH  - Arginase/administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - Carcinoma, Hepatocellular/*drug therapy
MH  - Chemistry, Pharmaceutical
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Liver Neoplasms/*drug therapy
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Polyethylene Glycols/*chemistry
MH  - Prospective Studies
MH  - *Quality of Life
MH  - Recombinant Proteins
MH  - Response Evaluation Criteria in Solid Tumors
EDAT- 2015/02/11 06:00
MHDA- 2016/01/20 06:00
CRDT- 2015/02/11 06:00
PHST- 2014/11/06 00:00 [received]
PHST- 2014/12/09 00:00 [accepted]
PHST- 2015/02/11 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2016/01/20 06:00 [medline]
AID - 10.1007/s10637-014-0200-8 [doi]
PST - ppublish
SO  - Invest New Drugs. 2015 Apr;33(2):496-504. doi: 10.1007/s10637-014-0200-8. Epub 
      2015 Feb 10.