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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 510 - 518 (9page)
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Purpose The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). Materials and Methods This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. Results A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). Conclusion OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.
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참고문헌 (26)
참고문헌 신청
El-Serag HB / 2011 / Hepatocellular carcinoma / N Engl J Med 365:1118~1127
정규원 / 2017 / Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2014 / Cancer Research and Treatment 49(2):292~305
Bruix J / 2011 / Management of hepatocellular carcinoma: an update / Hepatology 53:1020~1022
Llovet JM / 2008 / Sorafenib in advanced hepatocellular carcinoma / N Engl J Med 359:378~390
Cheng AL / 2009 / Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma : a phase III randomised, double-blind, placebo-controlled trial / Lancet Oncol 10:25~34
정규원 / 2017 / Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2014 / Cancer Research and Treatment 49(2):292~305
Bruix J / 2011 / Management of hepatocellular carcinoma: an update / Hepatology 53:1020~1022
Llovet JM / 2008 / Sorafenib in advanced hepatocellular carcinoma / N Engl J Med 359:378~390
Cheng AL / 2009 / Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma : a phase III randomised, double-blind, placebo-controlled trial / Lancet Oncol 10:25~34
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Cadmium-induced oxidative stress regulation of mitochondria STAT3
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Gallic Acid I nhibits STAT3 Phosphorylation and Alleviates DDS-induced Colitis via Regulating Cytokine Production
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