title: Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.
abstract: 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.
authors: Department of Medicine, The University of Hong Kong, Hong Kong, China, the@netvigator.com.
authors: Thomas
authors: T
authors: Yau
authors: Paul N
authors: PN
authors: Cheng
authors: Pierre
authors: P
authors: Chan
authors: Li
authors: L
authors: Chen
authors: Jimmy
authors: J
authors: Yuen
authors: Roberta
authors: R
authors: Pang
authors: Sheung Tat
authors: ST
authors: Fan
authors: Denys N
authors: DN
authors: Wheatley
authors: Ronnie T
authors: RT
authors: Poon
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D019540:Area Under Curve; D001119:Arginase / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000737:chemistry*; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins; D066066:Response Evaluation Criteria in Solid Tumors
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C574619:ARG1 protein, human; D001119:Arginase