https://scholars.lib.ntu.edu.tw/handle/123456789/580130
標題: | Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma | 作者: | ANN-LII CHENG Thongprasert S. Lim H.Y. Sukeepaisarnjaroen W. Yang T.-S. Wu C.-C. Chao Y. Chan S.L. Kudo M. Ikeda M. Kang Y.-K. Pan H. Numata K. Han G. Balsara B. Zhang Y. Rodriguez A.-M. Zhang Y. Wang Y. Poon R.T.P. |
公開日期: | 2016 | 出版社: | John Wiley and Sons Inc. | 卷: | 64 | 期: | 3 | 起(迄)頁: | 774-784 | 來源出版物: | Hepatology | 摘要: | Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and sorafenib, respectively. Common any-cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, respectively [P =.0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, respectively [P = 0.0002]). Conclusion: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774-784). ? 2016 by the American Association for the Study of Liver Diseases |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84987909452&doi=10.1002%2fhep.28600&partnerID=40&md5=630d69ed17343ab0f2f005f95013f9c0 https://scholars.lib.ntu.edu.tw/handle/123456789/580130 |
ISSN: | 0270-9139 | DOI: | 10.1002/hep.28600 | SDG/關鍵字: | alanine aminotransferase; aspartate aminotransferase; bilirubin; diuretic agent; dovitinib; platelet derived growth factor receptor; scatter factor; sorafenib; vasculotropin receptor 1; warfarin; abdominal distension; abdominal pain; acne; adult; advanced cancer; aged; alopecia; anemia; Article; ascites; cancer chemotherapy; cancer survival; clinical evaluation; comparative study; constipation; controlled study; coughing; decreased appetite; diarrhea; disease course; dizziness; drug dose escalation; drug dose reduction; drug efficacy; drug safety; drug withdrawal; dyspnea; fatigue; female; fever; gastrointestinal hemorrhage; hand foot syndrome; headache; hepatic encephalopathy; human; hypertension; hypoalbuminemia; insomnia; liver cell carcinoma; lung embolism; major clinical study; male; multicenter study; multiple cycle treatment; nausea; neutrophil count; open study; overall survival; peripheral edema; phase 2 clinical trial; priority journal; pruritus; randomized controlled trial; rash; side effect; stomatitis; thrombocytopenia; time to treatment; treatment duration; tumor growth; upper abdominal pain; vomiting |
顯示於: | 醫學系 |
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