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

Yang TS, Lu SN, Chao Y, Sheen IS, Lin CC, Wang TE, Chen SC, Wang JH, Liao LY, Thomson JA, Wang-Peng J, Chen PJ, Chen LT - Br. J. Cancer (2010)

Bottom Line: Both efficacy parameters were comparable between the two study arms.The major treatment-related adverse events were grades 1-2 local and/or allergic reactions.ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, LinKou Medical Center, Chang Gung University, Taoyuan 33305, Taiwan.

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 (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.

Show MeSH

Related in: MedlinePlus

Overall survival curves in patients with depletion of circulating arginine for ⩾4 weeks (orange line) and <4 weeks (blue line) of duration after ADI-PEG 20 treatment (P=0.251, log-rank test).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2965867&req=5

fig4: Overall survival curves in patients with depletion of circulating arginine for ⩾4 weeks (orange line) and <4 weeks (blue line) of duration after ADI-PEG 20 treatment (P=0.251, log-rank test).

Mentions: The proposed mechanism of action of ADI-PEG 20 treatment is the preferential starvation of tumour cells by arginine depletion, so the correlation between the duration of arginine depletion and OS was examined. Among the 61 subjects who had received at least one complete cycle (four doses) of treatment, the median survival of those with (n=36) and without (n=25) sustained depletion of plasma arginine level for 4 weeks was 10.0 (95% CI: 2.1–17.9) months and 5.8 (95% CI: 1.4–10.1) months respectively (P=0.251, log-rank test; Figure 4). Of the 36 patients showing depletion of plasma arginine for 4 weeks, 13 patients continued to show depletion of plasma arginine for 8 or more weeks. The median OS of these 13 patients was 15.2 months (95% CI: 1.2–29.1).


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

Yang TS, Lu SN, Chao Y, Sheen IS, Lin CC, Wang TE, Chen SC, Wang JH, Liao LY, Thomson JA, Wang-Peng J, Chen PJ, Chen LT - Br. J. Cancer (2010)

Overall survival curves in patients with depletion of circulating arginine for ⩾4 weeks (orange line) and <4 weeks (blue line) of duration after ADI-PEG 20 treatment (P=0.251, log-rank test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965867&req=5

fig4: Overall survival curves in patients with depletion of circulating arginine for ⩾4 weeks (orange line) and <4 weeks (blue line) of duration after ADI-PEG 20 treatment (P=0.251, log-rank test).
Mentions: The proposed mechanism of action of ADI-PEG 20 treatment is the preferential starvation of tumour cells by arginine depletion, so the correlation between the duration of arginine depletion and OS was examined. Among the 61 subjects who had received at least one complete cycle (four doses) of treatment, the median survival of those with (n=36) and without (n=25) sustained depletion of plasma arginine level for 4 weeks was 10.0 (95% CI: 2.1–17.9) months and 5.8 (95% CI: 1.4–10.1) months respectively (P=0.251, log-rank test; Figure 4). Of the 36 patients showing depletion of plasma arginine for 4 weeks, 13 patients continued to show depletion of plasma arginine for 8 or more weeks. The median OS of these 13 patients was 15.2 months (95% CI: 1.2–29.1).

Bottom Line: Both efficacy parameters were comparable between the two study arms.The major treatment-related adverse events were grades 1-2 local and/or allergic reactions.ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, LinKou Medical Center, Chang Gung University, Taoyuan 33305, Taiwan.

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 (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.

Show MeSH
Related in: MedlinePlus