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Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer.
- Source :
-
PloS one [PLoS One] 2015 Aug 14; Vol. 10 (8), pp. e0134731. Date of Electronic Publication: 2015 Aug 14 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.<br />Trial Registration: ClinicalTrials.gov NCT00917462.
- Subjects :
- Adenocarcinoma mortality
Adenocarcinoma pathology
Adult
Aged
Disease-Free Survival
Esophageal Neoplasms mortality
Esophageal Neoplasms pathology
Esophagogastric Junction drug effects
Female
Humans
Male
Middle Aged
Neoplasm Metastasis
Niacinamide therapeutic use
Sorafenib
Stomach Neoplasms mortality
Stomach Neoplasms pathology
Survival Analysis
Adenocarcinoma drug therapy
Antineoplastic Agents therapeutic use
Drug Resistance, Neoplasm drug effects
Esophageal Neoplasms drug therapy
Esophagogastric Junction pathology
Niacinamide analogs & derivatives
Phenylurea Compounds therapeutic use
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26275293
- Full Text :
- https://doi.org/10.1371/journal.pone.0134731