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: T-S Yang, S-N Lu, Y Chao, I-S Sheen, C-C Lin, T-E Wang, S-C Chen, J-H Wang, L-Y Liao, J A Thomson, J Wang-Peng, P-J Chen, L-T Chen
• Journal: British journal of cancer (Br J Cancer) Vol. 103 Issue 7 Pg. 954-60 (Sep 28 2010) ISSN: 1532-1827 [Electronic] England
• PMID: 20808309 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Polyethylene Glycols
• Arginine
• Hydrolases
• ADI PEG20

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Arginine (blood)
• Asian People
• Carcinoma, Hepatocellular (blood, drug therapy, mortality)
• Disease-Free Survival
• Female
• Humans
• Hydrolases (therapeutic use)
• Liver Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Retreatment