https://scholars.lib.ntu.edu.tw/handle/123456789/580072
標題: | A Phase I/Randomized Phase II Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nintedanib versus Sorafenib in Asian Patients with Advanced Hepatocellular Carcinoma | 作者: | Yen C.-J. Kim T.-Y. Feng Y.-H. Chao Y. Lin D.-Y. Ryoo B.-Y. Huang D.C.-L. Schnell D. Hocke J. Loemb? A.-B. ANN-LII CHENG |
關鍵字: | Advanced hepatocellular carcinoma; Angiokinase inhibitor; Dose-limiting toxicity; Maximum tolerated dose; Nintedanib; Sorafenib | 公開日期: | 2018 | 出版社: | S. Karger AG | 卷: | 7 | 期: | 2 | 起(迄)頁: | 165-178 | 來源出版物: | Liver Cancer | 摘要: | Background: Nintedanib is an oral, triple angiokinase inhibitor of vascular endothelial growth factor/platelet-derived growth factor/fibroblast growth factor receptors. This randomized, multicenter, open-label, phase I/II study evaluated the safety, pharmacokinetics, maximum tolerated dose (MTD) in terms of dose-limiting toxicities (DLTs), and efficacy of nintedanib versus sorafenib in Asian patients with unresectable advanced hepatocellular carcinoma (HCC). Patients and Methods: For the phase I portion, patients were stratified into two groups according to their alanine aminotransferase/aspartate aminotransferase (ALT/AST) and Child-Pugh score at baseline. For phase I, the primary endpoint was determination of the MTD in terms of DLTs. For phase II, patients with a Child-Pugh score of 5-6, an Eastern Cooperative Oncology Group performance score ?2, and an ALT/AST ?2× the upper limit of normal were enrolled and randomized 2: 1 to nintedanib 200 mg twice daily (b.i.d.) (the MTD determined in phase I) or sorafenib 400 mg b.i.d. continuously in 28-day cycles until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. The primary endpoint for phase II was time to progression (TTP) by central independent review (CIR; by Response Evaluation Criteria in Solid Tumors v1.0); the secondary endpoints included overall survival (OS). All analyses were exploratory. Results: The MTD was 200 mg in both groups. For phase II, 95 patients were randomized to nintedanib (n = 63) or sorafenib (n = 32). For nintedanib and sorafenib, respectively, the median CIR TTP was 2.8 vs. 3.7 months (hazard ratio [HR] = 1.21, 95% confidence interval [CI] 0.73-2.01) and the median OS 10.2 vs. 10.7 months (HR = 0.94, 95% CI 0.59-1.49). Nintedanib-treated patients had fewer grade 3 or higher AEs (56 vs. 84%), serious AEs (46 vs. 56%), and AEs leading to dose reduction (19 vs. 59%) and drug discontinuation (24 vs. 34%). AEs associated more frequently with nintedanib were vomiting and nausea, whereas those associated more frequently with sorafenib were ALT/AST increases, diarrhea, rash, and palmar-plantar erythrodysesthesia syndrome. Conclusions: Nintedanib showed numerically similar efficacy to sorafenib for CIR TTP and OS in Asian patients with advanced HCC and adequate liver function. AEs were generally manageable. ? 2018 S. Karger AG, Basel All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044076967&doi=10.1159%2f000486460&partnerID=40&md5=9cea784b13824deb32c23b69fcc05172 https://scholars.lib.ntu.edu.tw/handle/123456789/580072 |
ISSN: | 2235-1795 | DOI: | 10.1159/000486460 | SDG/關鍵字: | alanine aminotransferase; aspartate aminotransferase; nintedanib; sorafenib; abdominal distension; abdominal pain; adult; advanced cancer; aged; anemia; area under the curve; Article; ascites; Asian; asthenia; Child Pugh score; cohort analysis; constipation; controlled study; coughing; decreased appetite; diarrhea; disease exacerbation; drug absorption; drug dose reduction; drug efficacy; drug safety; drug tolerability; drug urine level; drug withdrawal; fatigue; female; fever; hand foot syndrome; human; hypertension; hyponatremia; inoperable cancer; liver cell carcinoma; liver failure; liver function; major clinical study; male; maximum concentration; maximum tolerated dose; multicenter study; multiple cycle treatment; nausea; overall survival; phase 1 clinical trial; phase 2 clinical trial; pleura effusion; priority journal; randomized controlled trial; rash; response evaluation criteria in solid tumors; single drug dose; skin manifestation; thrombocytopenia; time to maximum plasma concentration; treatment duration; treatment outcome; very elderly; vomiting |
顯示於: | 醫學系 |
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