Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial

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Anthracycline’s Effects on Heart Rate Variability in Children with Acute Lymphoblastic Leukemia: Early Toxicity Signs—Pilot Study

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m2). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters’ ratio also displayed a significant difference (p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity

Linifanib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: Results of a Randomized Phase III Trial

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 non-inferiority 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. (C) 2014 by American Society of Clinical Oncolog