title: A decrease in D-dimer concentration and an occurrence of skin rash as iatrogenic events and complementary predictors of survival in lung cancer patients treated with EGFR tyrosine kinase inhibitors.
abstract: BACKGROUND
  Progression of lung cancer is associated with some abnormalities in coagulation. The aim of the study was to determine the predictive and prognostic value of changes in D-dimer concentration in non-small cell lung cancer (NSCLC) patients on anti-EGFR targeted therapy.
  
  
  METHODS
  The analysis included fifty two NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs): erlotinib or gefitinib. All clinical data were collected before treatment and after 2 cycles (60days) of therapy and correlated with progression free and overall survival (PFS, OS).
  
  
  RESULTS
  Two iatrogenic events were noted within the first 60days of anti-EGFR treatment: typical skin rash in 38 (73.1%) and a decrease in D-dimer concentration in 26 (50%) patients. Multivariate analysis revealed a decrease of D-dimer concentration as the strongest factor associated with longer PFS (HR=0.39; 95%CI: 0.16-0.91; p=0.029) and OS (HR=0.33; 95%CI: 0.13-0.82, p=0.017) independently of skin rash, baseline level of D-dimer and other clinical characteristics. Coexisting a decrease in D-dimer concentration with an occurrence of skin rash correlated significantly with the positive objective response after 60days of anti-EGFR therapy (p=0.0175) and indicated the longest PFS (HR=0.31; 95%CI: 0.16-0.60, p=0.0005) as well as OS (HR=0.30; 95%CI: 0.15-0.59, p=0.0005).
  
  
  CONCLUSIONS
  Adverse events may predict the outcomes of cancer patients. Apart from skin rash, change in D-dimer concentration may be valuable parameter in creation of predictive and prognostic models in NSCLC patients receiving anti-EGFR targeted therapy.
authors: Lung & Thoracic Tumors Department, The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology, Warszawa, Poland.
authors: Magdalena
authors: M
authors: Zaborowska-Szmit
authors: Lung & Thoracic Tumors Department, The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology, Warszawa, Poland.
authors: Dariusz M
authors: DM
authors: Kowalski
authors: Lung & Thoracic Tumors Department, The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology, Warszawa, Poland.
authors: Aleksandra
authors: A
authors: Piórek
authors: Lung & Thoracic Tumors Department, The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology, Warszawa, Poland.
authors: Maciej
authors: M
authors: Krzakowski
authors: Department of Pulmonary Circulation and Thromboembolic Diseases, Centre of Postgraduate Medical Education, European Health Centre Otwock, Otwock, Poland. Electronic address: s.szmit@gmail.com.
authors: Sebastian
authors: S
authors: Szmit
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D005076:Exanthema / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D000077156:Gefitinib; D006801:Humans; D007049:Iatrogenic Disease; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate / Q000639:trends
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005338:Fibrin Fibrinogen Degradation Products; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C036309:fibrin fragment D; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: D-dimer; EGFR inhibitors; Lung cancer; Overall survival; Progression free survival; Skin rash