RESUMEN
PURPOSE: Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer. PATIENTS AND METHODS: This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity. RESULTS: Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET. CONCLUSION: Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00917462.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Unión Esofagogástrica/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Niacinamida/uso terapéutico , Sorafenib , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
Use of PET is widespread and increasing in the United States, mainly for oncologic applications. In November 2006, the National Comprehensive Cancer Network (NCCN) gathered a panel of experts to review the literature and develop clinical recommendations for using PET scans in lymphoma and non-small cell lung, breast, and colorectal cancers. However, because its use is not restricted to these diseases, and evidence is accumulating for its application in other types of cancers, NCCN convened a second meeting in December 2008 to expand on the initial report. A multidisciplinary panel met to discuss the current data on PET application for various tumor types, including genitourinary, gynecologic, pancreatic, hepatobiliary, thyroid, brain, small cell lung, gastric, and esophageal cancers, and sarcoma and myeloma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, the role of PET in oncology, principles of PET use, emerging applications, and possible future developments.