國家衛生研究院 NHRI:Item 3990099045/10771
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    題名: A phase II study of Arginine Deiminase (ADI-PEG20) in relapsed/refractory or poor-risk acute myeloid leukemia patients
    作者: Tsai, HJ;Jiang, SS;Hung, WC;Borthakur, G;Lin, SF;Pemmaraju, N;Jabbour, E;Bomalaski, JS;Chen, YP;Hsiao, HH;Wang, MC;Kuo, CY;Chang, H;Yeh, SP;Cortes, J;Chen, LT;Chen, TY
    貢獻者: National Institute of Cancer Research
    摘要: Exogenous arginine is required for growth in some argininosuccinate synthetase (ASS)-deficient cancers. Arginine deiminase (ADI) inhibits growth in various ASS-deficient cancers by depleting arginine. The efficacy of pegylated ADI (ADI-PEG20) in relapsed/refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phase II trial (NCT01910012 (10/07/2013), https://clinicaltrials.gov/ct2/show/NCT01910012?term=ADI-PEG20&rank=12). Despite almost all pre-treatment tumor samples showing ASS deficiency, the best response among 21 evaluable patients was complete response (CR) in 2 (9.5%) and stable disease in 7 (33.3%), yielding a disease control rate (DCR) of 42.9%. The response durations of the two patients with CR were 7.5 and 8.8 months. DCR was correlated with a median of 8 weeks of arginine depletion to <= 10 mu M. Using whole transcriptome sequencing, we compared gene expression profiling of pre- and post-treatment bone marrow samples of the two responders and three non-responders. The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered potential predictors of response to ADI-PEG20. These results suggest that ASS deficiency is a prerequisite but not a sufficient condition for response to ADI-PEG20 monotherapy in AML. Predictive biomarkers and mechanistic explorations will be critical for identifying appropriate patients for future AML trials of ADI-PEG20.
    日期: 2017-09
    關聯: Scientific Reports. 2017 Sep;7:Article number 11253.
    Link to: http://dx.doi.org/10.1038/s41598-017-10542-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000410295300009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85029282891
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