Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.

GOALS AND BACKGROUND: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. METHODS: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Fifteen patients presented without LCI or with LCI Child- Pugh A, 15/4 patients had LCI Child-Pugh B/C. Barcelona Clinic Liver Cancer stage was B/C/D in 4/22/8 patients. During treatment period (median 2.2 mo), therapy was discontinued in 61.8% of patients due to tumor progression (32.3%), death (17.6%), AEs (8.8%), or noncompliance (2.9%). Most common grade 3/4 AEs included liver dysfunction (23.5%), diarrhea (14.7%), increased lipase (8.8%), fatigue (8.8%), and hand-foot skin reaction (5.9%). Worsening liver dysfunction/failure was more frequent (P=0.036) in patients with LCI Child-Pugh B/C compared with patients with maintained liver function (no LCI/LCI Child-Pugh A). Median overall survival was 7.2 months for patients with maintained liver function versus 3.3/3.4 months for patients with LCI Child-Pugh B/C. CONCLUSIONS: These data do not support the use of sorafenib in patients with LCI Child-Pugh C, and patients with LCI Child-Pugh B should be treated with caution until larger trials provide more safety data and a clinically relevant survival benefit under sorafenib therapy.

Cerebral infarction: incidence and risk factors after diagnostic and interventional cardiac catheterization--prospective evaluation at diffusion-weighted MR imaging.

PURPOSE: To prospectively evaluate incidence of clinically silent and clinically apparent embolic cerebral infarction following diagnostic and interventional coronary angiography and associated risk factors. MATERIALS AND METHODS: Written informed consent was obtained from all patients, and the study was approved by the research ethics committee of University of Heidelberg, Germany. Fifty-two patients, including 37 men (mean age, 66.1 years +/- 11.9 [standard deviation]) and 15 women (mean age, 65.3 years +/- 10.3), undergoing elective cardiac catheterization were examined 3-26 hours (mean, 15.3 hours +/- 6) before and 12-48 hours (mean, 25.9 hours +/- 10.4) after cardiac catheterization. Magnetic resonance imaging protocol included isotropic and anisotropic diffusion-weighted single-shot echo-planar sequences. T2-weighted turbo spin-echo and T1-weighted spin-echo sequences also were performed. Apparent diffusion coefficient maps were calculated to exclude false-positive reading results on diffusion-weighted images because of T2 shine-through effect. Images were assessed by two experienced radiologists blinded to clinical data. Cardiac catheterization was performed by 11 experienced cardiologists to exclude operator-related risk. A neurologic examination according to the National Institutes of Health Stroke Scale and Barthel index was performed by a senior cardiologist before acquisition of each image. Sixteen clinical and angiographic variables were analyzed with univariate analysis for ability to predict occurrence of cerebral infarction. RESULTS: No embolic cerebral lesions could be detected at diffusion-weighted imaging before catheterization. After coronary angiography, seven (15%) of 48 patients demonstrated nine focal cerebral infarcts affecting anterior and posterior circulation. Patients remained asymptomatic. Of all tested variables, only duration of the procedure was identified as an independent predictor of occurrence of cerebral infarction (P < .05). CONCLUSION: In this prospective study, asymptomatic cerebral infarction following cardiac catheterization occurred in 15% of patients in whom duration of the procedure was significantly longer than in those without infarction (P = .017).