RESUMEN
BACKGROUND: No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. METHODS: In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. RESULTS: At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. CONCLUSIONS: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.)
Asunto(s)
Bencenosulfonatos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Quinasas raf/antagonistas & inhibidores , Anciano , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/efectos adversos , Piridinas/efectos adversos , Sorafenib , Análisis de SupervivenciaRESUMEN
Liver transplantation is currently an accepted first-line treatment for patients with end-stage acute or chronic liver disease, but postoperative complications may limit the long-term success of transplantation. The most common and most clinically significant complications are arterial and venous thrombosis and stenosis, biliary disorders, fluid collections, neoplasms, and graft rejection. Early diagnosis is crucial to the successful management of all these complications, and imaging plays an important role in the diagnosis of all but graft rejection. A multimodality approach including ultrasonography and cross-sectional imaging studies often is most effective for diagnosis. Each imaging modality has specific strengths and weaknesses, and the diagnostic usefulness of a modality depends mainly on the patient's characteristics, the clinical purpose of the imaging evaluation, and the expertise of imaging professionals.