Tumor Biology

, Volume 36, Issue 12, pp 9215–9222 | Cite as

High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib

  • Ondrej Fiala
  • Milos Pesek
  • Jindrich Finek
  • Ondrej Topolcan
  • Jaroslav Racek
  • Marek Minarik
  • Lucie Benesova
  • Zbynek Bortlicek
  • Alexandr Poprach
  • Tomas Buchler
Research Article


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.


C-reactive protein Lung cancer NSCLC EGFR-TKI Erlotinib Prediction Biomarker 



The authors would like to thank all the patients who voluntarily took part in the observational, population-based registry TULUNG. This study is supported by the Ministry of Health, Czech Republic [conceptual development of research organizations: Faculty Hospital in Pilsen - FNPl (00669806) and Masaryk Memorial Cancer Institute - MMCI (00209805)] and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund.

Conflicts of interest

JF has received honoraria from AstraZeneca, Roche and Novartis for consultations and lectures unrelated to this project. TB has received honoraria from Roche for consultations and lectures unrelated to this project. AP has received honoraria from GSK, Roche and Bayer for consultations and lectures unrelated to this project. OF, MP, OT, MM, LB, JR and ZB declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ondrej Fiala
    • 1
    • 2
  • Milos Pesek
    • 3
  • Jindrich Finek
    • 1
  • Ondrej Topolcan
    • 4
  • Jaroslav Racek
    • 5
  • Marek Minarik
    • 6
    • 7
  • Lucie Benesova
    • 5
  • Zbynek Bortlicek
    • 8
  • Alexandr Poprach
    • 9
  • Tomas Buchler
    • 10
  1. 1.Department of Oncology and Radiotherapy, Medical School and Teaching Hospital in PilsenCharles University in PraguePilsenCzech Republic
  2. 2.Biomedical Center, Faculty of Medicine in PilsenCharles University in PraguePilsenCzech Republic
  3. 3.Department of Pneumology, Medical School and Teaching Hospital in PilsenCharles University in PraguePilsenCzech Republic
  4. 4.Department of Nuclear Medicine, Medical School and Teaching Hospital in PilsenCharles University in PraguePilsenCzech Republic
  5. 5.Institute of Clinical Biochemistry and Hematology, Medical School and Teaching Hospital in PilsenCharles University in PraguePilsenCzech Republic
  6. 6.Center for Applied Genomics of Solid TumoursGenomac Research InstitutePragueCzech Republic
  7. 7.Department of Analytical Chemistry, Faculty of SciencesCharles University in PraguePilsenCzech Republic
  8. 8.Institute of Biostatistics and Analysis, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  9. 9.Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  10. 10.Department of Oncology and First Faculty of MedicineCharles University and Thomayer HospitalPragueCzech Republic

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