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

Tsai Sheng Yang, Sheng Nan Lu, Yee Chao, I. Shyan Sheen, Chun Lin Chen, Tsang En Wang, Shinn Cherng Chen, Jing Houng Wang, Li Ying Liao, Alan J. Thomson, Jacqueline Whang-Peng, Pei Jer Chen, Li Tzong Chen

Research output: Contribution to journalArticle

90 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)954-960
Number of pages7
JournalBritish Journal of Cancer
Volume103
Issue number7
DOIs
Publication statusPublished - Sep 28 2010
Externally publishedYes

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Hepatocellular Carcinoma
Confidence Intervals
Arginine
Argininosuccinate Synthase
Survival
Intramuscular Injections
Population
Hypersensitivity
Therapeutics
ADI PEG20

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients. / Yang, Tsai Sheng; Lu, Sheng Nan; Chao, Yee; Sheen, I. Shyan; Chen, Chun Lin; Wang, Tsang En; Chen, Shinn Cherng; Wang, Jing Houng; Liao, Li Ying; Thomson, Alan J.; Whang-Peng, Jacqueline; Chen, Pei Jer; Chen, Li Tzong.

In: British Journal of Cancer, Vol. 103, No. 7, 28.09.2010, p. 954-960.

Research output: Contribution to journalArticle

Yang, TS, Lu, SN, Chao, Y, Sheen, IS, Chen, CL, Wang, TE, Chen, SC, Wang, JH, Liao, LY, Thomson, AJ, Whang-Peng, J, Chen, PJ & Chen, LT 2010, 'A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients', British Journal of Cancer, vol. 103, no. 7, pp. 954-960. https://doi.org/10.1038/sj.bjc.6605856
Yang, Tsai Sheng ; Lu, Sheng Nan ; Chao, Yee ; Sheen, I. Shyan ; Chen, Chun Lin ; Wang, Tsang En ; Chen, Shinn Cherng ; Wang, Jing Houng ; Liao, Li Ying ; Thomson, Alan J. ; Whang-Peng, Jacqueline ; Chen, Pei Jer ; Chen, Li Tzong. / A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients. In: British Journal of Cancer. 2010 ; Vol. 103, No. 7. pp. 954-960.
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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 (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.",
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T1 - A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

AU - Yang, Tsai Sheng

AU - Lu, Sheng Nan

AU - Chao, Yee

AU - Sheen, I. Shyan

AU - Chen, Chun Lin

AU - Wang, Tsang En

AU - Chen, Shinn Cherng

AU - Wang, Jing Houng

AU - Liao, Li Ying

AU - Thomson, Alan J.

AU - Whang-Peng, Jacqueline

AU - Chen, Pei Jer

AU - Chen, Li Tzong

PY - 2010/9/28

Y1 - 2010/9/28

N2 - 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 (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.

AB - 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 (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.

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KW - argininosuccinate synthetase

KW - hepatocellular carcinoma

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