Currently, second-line chemotherapy is the standard of care for platinum-pretreated NSCLC even though its efficiency is poor ,  and . Docetaxel and pemetrexed are currently the standard second-line chemotherapy agents for NSCLC.
Treatment with pemetrexed generally results in clinically equivalent efficacy outcomes with docetaxel in the second-line treatment of patients with advanced NSCLC . However, pemetrexed and docetaxel only produced overall response rates (ORRs) of 9.1% and 8.8% with a median survival time of 8.3 and 7.9 months, respectively, Selleck ATM/ATR inhibitor in platinum-pretreated NSCLC . The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib have also been used as standard second-line agents in treating NSCLC. Sensitivity to EGFR TKIs is dependent on the activation of the EGFR pathway or the presence of EGFR-interacting proteins . Studies showed that no significant differences in efficacy were noted between patients treated with TKIs and those treated with docetaxel or pemetrexed in platinum-pretreated NSCLC ,  and . Therapeutic inhibition of EGFR with TKIs has resulted in favorable response rates only in 11.14% to 15.25% of platinum-pretreated NSCLC, mostly because the EGFR mutation or gene amplification rate is only 16.6% in NSCLC  and . In addition, median survival
of Selleck BTK inhibitor 7.6 months for gefitinib in platinum-pretreated NSCLC and 5.3 months for erlotinib in platinum-resistant NSCLC indicate the desperate need for novel approaches to treat the patient population , ,  and . We previously found that 5% ethanol-cisplatin injected intratumorally could eradicate cisplatin-resistant lung tumors and extend survival by improved killing of lung CSCs in mice . We believe that 5% ethanol improves the efficacy of CSC killing by inhibiting breast cancer resistance protein (BRCP/ABCG2) Bay 11-7085 drug transporter function and by improving the penetration of cisplatin into the tumor cells . On the basis of our model organism studies, it is possible that computed tomography (CT)–guided percutaneous fine-needle 5% ethanol-cisplatin intratumoral
injection (CT-PFNECII) might also regress platinum-pretreated or even platinum-resistant tumors in patients with NSCLC by killing chemoresistant cancer stem cells and cancer cells. Furthermore, it is possible that the residual unkilled but damaged tumor cells after 5% ethanol-cisplatin treatment might be more fragile and sensitive to systemic second-line chemotherapy agents. Thus, combination of CT-PFNECII with systemic second-line chemotherapy might provide a new way to improve survival of this patient population. This study is aimed to investigate the efficacy and safety of CT-PFNECII combined with second-line chemotherapy in patients with platinum-pretreated stage IV NSCLC. The study protocol was approved by the Institutional Review Boards of the No.