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.PEI-JER CHENChen L.-T.2021-07-032021-07-0320100007-0920https://www.scopus.com/inward/record.uri?eid=2-s2.0-77957245576&doi=10.1038%2fsj.bjc.6605856&partnerID=40&md5=36bb4bf4fc116dcff10296a68d247921https://scholars.lib.ntu.edu.tw/handle/123456789/568546Background: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 (P0.251, 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. ? 2010 Cancer Research UK. All rights reserved.arginine; arginine deiminase; argininosuccinate synthetase; hepatocellular carcinoma; polyethylene glycol[SDGs]SDG3adi peg 20; alpha fetoprotein; antineoplastic agent; pegylated arginine deiminase; unclassified drug; antineoplastic agent; arginine; hydrolase; macrogol derivative; pegargiminase; adult; aged; allergy; anemia; article; cancer control; clinical trial; controlled clinical trial; controlled study; diarrhea; drug activity; drug efficacy; drug fever; drug hypersensitivity; fatigue; female; hepatitis C; human; hyperammonemia; hyperuricemia; immunogenicity; injection site reaction; liver cell carcinoma; major clinical study; male; multicenter study; multiple cycle treatment; overall survival; phase 2 clinical trial; priority journal; progression free survival; pruritus; randomized controlled trial; rash; treatment response; Asian continental ancestry group; blood; Carcinoma, Hepatocellular; disease free survival; Liver Neoplasms; middle aged; mortality; retreatment; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Arginine; Asian Continental Ancestry Group; Carcinoma, Hepatocellular; Disease-Free Survival; Female; Humans; Hydrolases; Liver Neoplasms; Male; Middle Aged; Polyethylene Glycols; Retreatmentjournal article10.1038/sj.bjc.6605856208083092-s2.0-77957245576