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
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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