title: Effectiveness of erlotinib as a second line therapy for patients with epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC): our clinical experience.
abstract: OBJECTIVE
  The aim of this study was to evaluate tumour response, QoL and adverse effects of erlotinib, EGFR tyrosine kinase inhibitor (TKI), as a second line therapy for patients with EGFR mutation in NSCLC, after failure of previous first-line therapy.
  
  
  METHODS
  During the year 2010-11, 5 patients were enrolled in this study for testing EGFR mutations, after conditions for testing were created in Macedonia. We screened 5 patients for EGFR mutations by direct sequencing of exons 18 to 21, by retrospective analysis of their previous biopsy samples. Three of the patients were men and two of the patients were women. Two of the males were former smokers and one male and both females had never smoked. All the patients who were enrolled in the study had histologically proven adenocarcionoma. the patients started with erlotinib 150 mg, one tablet per day, after failure on previous first-line platinum-based chemotherapy, with or without surgery and radiotherapy. Assessment of tumour response was according to RECIST criteria at the follow-up visits every 4 weeks. We analysed tumour response from the beginning with erlotinib until tumuor progression or detection of severe toxicity. Assessment was performed only for those patients with EGFR mutations. Assessment of QoL was performed by patients' subjective answers, as subjective improvement and without subjective improvements. Adverse effects were applied according to WHO criteria.
  
  
  RESULTS
  Tissue was available for all 5 cases, two (40%) of which were found to harbour an EGFR mutation, identified as exon 19 deletions. Two patients responded to therapy. A complete response was seen in a female patient for 37 months. Progressive disease was the reason for stopping erlotinib after 37 months and starting third-line therapy. A partial response in one male patient was assessed for 30 months and is still in follow up. This patient is still alive and in good condition. The two patients reported subjective improvements during treatment with erlotinib. Skin rash was grade 2-3, and diarrhoea was grade 1-2. Both patients complained of hair loss, but without complete alopecia.
  
  
  CONCLUSIONS
  Considering our clinical results, we recommend target therapy with erlotinib for patients with NSCLC and EGFR mutations as a second-line treatment. Our excellent results encouraged us to require prospective tissue procurement for all patients in Macedonia. This may in fact require a shift in diagnostic practice, from the current emphasis on fine-needle aspiration, which often provides insufficient material for molecular analysis, to obtaining more substantial biopsies and to provide this treatment as first-line for selected patients.
authors.affiliation: University Radiotherapy and Oncology Clinic,  Faculty of Medicine, Skopje, R. Macedonia.
authors.forename: S
authors.initials: S
authors.lastname: Crvenkova
authors.forename: Lj
authors.initials: Lj
authors.lastname: Ivkovski
authors.forename: A
authors.initials: A
authors.lastname: Dimovski
authors.forename: B
authors.initials: B
authors.lastname: Kaeva
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011788:Quality of Life; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors