國家衛生研究院 NHRI:Item 3990099045/11146
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 856839      Online Users : 938
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11146


    Title: Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma
    Authors: Abou-Alfa, G;Qin, S;Ryoo, BY;Lu, SN;Yen, CJ;Feng, YH;Lim, HY;Izzo, F;Colombo, M;Sarker, D;Bolondi, L;Vaccaro, G;Harris, WP;Chen, Z;Hubner, RA;Meyer, T;Sun, W;Harding, JJ;Hollywood, EM;Ma, J;Wan, PJ;Ly, M;Bomalaski, J;Johnston, A;Lin, CC;Chao, Y;Chen, LT
    Contributors: National Institute of Cancer Research
    Abstract: Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme - arginine deiminase - conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and Patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2:1 to ADI-PEG 20 18 mg/m2 vs. placebo intramuscular (IM) injection weekly. The primary endpoint was overall survival (OS), with 93% power to detect a 4 to 5.6 months increase in median OS (1-sided alpha = 0.025). Secondary endpoints included progression-free survival (PFS), safety, and arginine correlatives. Results: 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 vs 7.4 for placebo (p = 0.88, HR = 1.02) and median PFS 2.6 months vs. 2.6 (p = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in less than 5% of patients. Two patients on ADI-PEG 20 had >/= grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 vs. 10.4% on placebo, none related to therapy. Post-hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials (NCT 01287585).
    Date: 2018-06
    Relation: Annals of Oncology. 2018 Jun;29(6):1402-1408.
    Link to: http://dx.doi.org/10.1093/annonc/mdy101
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-7534&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000438508100015
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85050800680
    Appears in Collections:[Li-Tzong Chen] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    PUB29659672.pdf570KbAdobe PDF190View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback