title: A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients.
abstract: BACKGROUND
  Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients.
  
  
  METHODS
  Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m(-2). The primary end point was disease-control rate (DCR).
  
  
  RESULTS
  Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions.
  
  
  CONCLUSIONS
  ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, LinKou Medical Center, Chang Gung University, Taoyuan 33305, Taiwan.
authors.forename: T-S
authors.initials: TS
authors.lastname: Yang
authors.forename: S-N
authors.initials: SN
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Chao
authors.forename: I-S
authors.initials: IS
authors.lastname: Sheen
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.forename: T-E
authors.initials: TE
authors.lastname: Wang
authors.forename: S-C
authors.initials: SC
authors.lastname: Chen
authors.forename: J-H
authors.initials: JH
authors.lastname: Wang
authors.forename: L-Y
authors.initials: LY
authors.lastname: Liao
authors.forename: J A
authors.initials: JA
authors.lastname: Thomson
authors.forename: J
authors.initials: J
authors.lastname: Wang-Peng
authors.forename: P-J
authors.initials: PJ
authors.lastname: Chen
authors.forename: L-T
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000097:blood; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D019233:Retreatment
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001120:Arginine; D006867:Hydrolases; C512527:ADI PEG20
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