Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma
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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.
KeywordsAdvanced HCC Arginine Arginase Peg-rhArg1
Bio-Cancer Treatment International Limited and the University of Hong Kong Hepatocellular Carcinoma Research Grant.
Potential conflicts of interest
Drs Thomas Yau, Pierre Chan, Jimmy Yuen, Roberta Pang, Professor Sheung Tat Fan and Professor Ronnie Poon report no potential conflict of interest.
Dr Paul Cheng is the chief executive officer of Bio-Cancer Treatment International Limited. Dr Li Chen is the chief technical officer of Bio-Cancer Treatment International Limited. Professor Denys Wheatley is the chief scientific officer of Bio-Cancer Treatment International Limited.
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