title: High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.
abstract: Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice.
authors.affiliation: Department of Oncology and Radiotherapy, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, alej Svobody 80, 304 60, Pilsen, Czech Republic. fiala.o@centrum.cz.|Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. fiala.o@centrum.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Fiala
authors.affiliation: Department of Pneumology, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Pesek
authors.affiliation: Department of Oncology and Radiotherapy, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, alej Svobody 80, 304 60, Pilsen, Czech Republic.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Finek
authors.affiliation: Department of Nuclear Medicine, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Topolcan
authors.affiliation: Institute of Clinical Biochemistry and Hematology, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Racek
authors.affiliation: Center for Applied Genomics of Solid Tumours, Genomac Research Institute, Prague, Czech Republic.|Department of Analytical Chemistry, Faculty of Sciences, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Minarik
authors.affiliation: Institute of Clinical Biochemistry and Hematology, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Benesova
authors.affiliation: Institute of Biostatistics and Analysis, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Bortlicek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Poprach
authors.affiliation: Department of Oncology and First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buchler
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D002097:C-Reactive Protein; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Biomarker; C-reactive protein; EGFR-TKI; Erlotinib; Lung cancer; NSCLC; Prediction