Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in Patients with Advanced Non–Small-Cell Lung Cancer Receiving Sorafenib
Autor: | Peter L. Choyke, Liqiang Xi, Jeremy Force, Corrine Keen, Mark Raffeld, Martin Gutierrez, Ariel Lopez-Chavez, Baris Turkbey, Liang Cao, Ronan J. Kelly, Seth M. Steinberg, John J. Wright, Shivaani Kummar, Yunkai Yu, Arun Rajan, Giuseppe Giaccone |
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Rok vydání: | 2011 |
Předmět: |
Male
Oncology Cancer Research Pathology Lung Neoplasms Pyridines Angiogenesis Angiogenesis Inhibitors medicine.disease_cause Tyrosine-kinase inhibitor Carcinoma Non-Small-Cell Lung Aged 80 and over Neovascularization Pathologic Benzenesulfonates Middle Aged Sorafenib Prognosis ErbB Receptors Tolerability Cytokines Female KRAS medicine.drug Adult Niacinamide Proto-Oncogene Proteins B-raf medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions medicine.drug_class Antineoplastic Agents Disease-Free Survival Article Proto-Oncogene Proteins p21(ras) Proto-Oncogene Proteins Internal medicine Biomarkers Tumor medicine Carcinoma Humans Lung cancer Protein Kinase Inhibitors neoplasms Aged business.industry Phenylurea Compounds Cancer medicine.disease Genes ras Mutation ras Proteins business Magnetic Resonance Angiography |
Zdroj: | Clinical Cancer Research. 17:1190-1199 |
ISSN: | 1557-3265 1078-0432 |
Popis: | Purpose: Sorafenib, a multikinase inhibitor targeting Raf and VEGFR, has shown activity in unselected patients with non–small-cell lung cancer (NSCLC). At present there are no validated biomarkers indicative of sorafenib activity. Experimental Design: Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects. KRAS mutation status (N = 34), angiogenesis markers (VEGF, bFGF, FLT-1, PLGF-1) and imaging with DCE-MRI (dynamic contrast enhanced MRI) to determine early changes in tumor vascular characteristics were evaluated. Three parameters Ktrans, Kep, and Ve were measured by DCE-MRI at baseline and day 14 of cycle 1. Cytokine analysis was done on days 0, 14, 28, and 54. Results: Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial. In 34 evaluable patients, 2 had partial responses and 20 had stable disease for 3 to 17 months, a disease control rate of 65%. The median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 11.6 months. Toxicity was consistent with the known side effects of sorafenib. KRAS (32%) and EGFR mutations (22%) showed no correlation with response, PFS, or OS. Kep, was significant in predicting an improvement in OS (P = 0.035) and PFS (P = 0.029). Cytokine analysis demonstrated an improved OS for bFGF day 0 (6 pg/mL; P = 0.042), whereas a PFS benefit was seen with bFGF at day 28 (6; P = 0.028). Conclusions: KRAS and EGFR mutational status showed no correlation with response, PFS, or OS. Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition. Clin Cancer Res; 17(5); 1190–9. ©2011 AACR. |
Databáze: | OpenAIRE |
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