Background/aim: We have previously reported that low expression of excision repair cross-complementing-1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase-M1 (RRM1) is indicative of a favorable prognosis in patients with c-N2,3 non-small cell lung cancer (NSCLC) treated with surgery after induction chemoradiotherapy. In the present study, we prospectively explored the tailor-made treatment menu for induction chemotherapy according to the status of biomarkers, and evaluated the biomarker status pre- and post-chemotherapy.
Patients and methods: Twenty-five patients with pathologically-proven NSCLC who were not appropriate candidates for initial surgery were enrolled (October 2010 to June 2012, stage IIIA/B/IV1a/1b;14/5/2/4 respectively). Immunohistochemistry was performed to evaluate intratumoral expression of biomarkers. Epidermal growth factor receptor (EGFR) mutation was evaluated by direct sequencing. Two to four cycles of chemotherapy were performed with or without concurrent radiation (50 Gy).
Results: Docetaxel (n=12), pemetrexed (n=4), S-1 (n=4), docetaxel-plus-bevacizumab (n=3), and pemetrexed-plus-bevacizumab (n=2), in combination with platinum were selected for the therapeutic regimen. Twenty-one (84.0%) patients exhibited good partial response, and underwent complete resection without major morbidity or mortality. Of these 21 patients, four achieved a pathologically-complete response (PCR), and 10 achieved a major pathological response. The 3-year overall survival rate was 58.7% for the 25 patients overall, and the 2-year overall survival rate was 73.6% for patients who underwent surgery. Among the 17 patients who underwent resection (except for four with PCR), the status of ERCC1, tubulin, TYMS, RRM1 and EGFR changed markedly after chemotherapy in six patients, eleven patients, eight patients, nine patients and one patient, respectively.
Conclusion: Chemotherapy followed by surgery on the basis of biomarker examination is a challenging approach for patients with advanced NSCLC who otherwise have poor outcomes. Post-chemotherapy biomarker status changed markedly in many cases.
Keywords: Chemotherapy; biomarker; lung cancer biology; lung cancer surgery.