OBJECTIVETo investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer (NSCLC) treated with iressa.

METHODSFrom May 2002 to Feb. 2005, iressa was orally administered at a dose of 250 mg once daily for 106 advanced stage NSCLC patients until occurrence of disease progression or intolerable toxicity. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 24 of EGFR. Exon 18 to 24 of EGFR were amplified by nest PCR, sequenced and analyzed from both sense and antisence directions.

RESULTSPrimary NSCLC tissue specimens consisted of 25 frozen tissue blocks and 81 paraffin-embedded tumor tissue blocks from 106 consecutive NSCLC patients. Mutation was found to be more frequent in the adenocarcinoma than in the squamous cell carcinoma (35.9% vs 14.3%, P =0.033). Mutation was identified in 32 patients (30.2%). Response rate to iressa was 71.9% in the patients with EGFR mutation versus 13.5% in those without mutation (P <0.01). Compared with the patients without EGFR mutation, those with mutation had longer overall survival (median, 13.45 vs. 5.25 months; P<0.01) and median time to progression (median, 8.35 vs. 3.0 months; P <0.01).

CONCLUSIONEGFR mutation may be positively correlated with the response and survival in advanced stage Chinese NSCLC patient treated with iressa.