A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

作者：Yang T S; Lu S N; Chao Y; Sheen I S^*; Lin C C; Wang T E; Chen S C; Wang J H; Liao L Y; Thomson J A; Wang Peng J; Chen P J; Chen L T

来源：British Journal of Cancer, 2010, 103(7): 954-960.

DOI：10.1038/sj.bjc.6605856

• arginine
• arginine deiminase
• hepatocellular carcinoma
• polyethylene glycol
• argininosuccinate synthetase

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 IUm(-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. British Journal of Cancer (2010) 103, 954-960. doi:10.1038/sj.bjc.6605856 www.bjcancer.

• 出版日期2010-9-28
• 单位长春大学