Purpose This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy. Patients and Methods Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1. Results We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P < .001). Conclusion Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib.
The 8-week yoga exercise program developed in this study effectively reduced fatigue in patients with breast cancer but did not reduce depression or anxiety. Oncology nurses should strengthen their clinical health education and apply yoga to reduce the fatigue experienced by patients with breast cancer who undergo adjuvant chemotherapy.
249 Background: Linifanib (ABT-869; Lin) is a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase families. In a phase II trial in patients (pts) with advanced HCC, Lin showed clinical activity (objective response rate [ORR] 10.5% in Child-Pugh A [CPA] pts). This open-label, global phase 3 trial evaluated Lin versus sorafenib (Sor) as first-line therapy in pts with advanced CPA HCC (NCT01009593). Methods: Pts were randomized 1:1 to Lin 17.5 mg QD or Sor 400 mg BID and stratified by region (non-Asia/Japan/rest of Asia), ECOG performance status (0/1), vascular invasion or extrahepatic spread (yes/no) and HBV infection (yes/no). The primary efficacy endpoint was overall survival (OS); both non-inferiority (margin 1.0491) and superiority hypotheses were to be tested. Secondary efficacy endpoints included time to progression (TTP) and ORR, using RECIST v1.1. AE severity was graded using NCI-CTCAE v4.0. Results: 1035 pts (median age 60 y, 68% Asian, 65% ECOG 0, 49% HBV, 70% vascular invasion or extrahepatic spread) were randomized at 149 sites in 26 countries. Hazard ratio (HR) for OS was 1.046 (95% CI: 0.896, 1.221). Median OS (95% CI) was 9.1 months (m) (8.1, 10.2) on Lin and 9.8 m (8.3, 11.0) on Sor. For all pre-specifed subgroup analyses, OS HRs ranged from 0.793-1.119, and the 95% CI contained 1.0. TTP HR was 0.759 (95% CI: 0.643, 0.895; p=0.001) favoring Lin. Median TTP (95% CI) was 5.4 m (4.2, 5.6) on Lin and 4.0 m (2.8. 4.2) on Sor. ORR was 13.0% on Lin and 6.9% on Sor. Grade 3/4 AEs, serious AEs and AEs leading to discontinuations, dose interruptions and reductions were more frequent on Lin versus Sor (all p<0.001). Conclusions: Lin and Sor resulted in similar OS in advanced HCC. Predefined superiority and non-inferiority OS boundaries were not met for Lin. Secondary endpoints (TTP and ORR) favored Lin while safety results favored Sor. Clinical trial information: NCT01009593.
Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.
Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.
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