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Abstract
Background: Erlotinib is a validated drug “for the treatment of patients affected by advanced unresectable non small cell lung cancer (NSCLC) with EGFR mutations”. We want to focus on potential functional benefits deriving from a combined therapy containing TKI (erlotinib) and a nicotinic partial agonist (varenicicline) in smokers. Methods: we analyzed the records of patients affected by NSCLC treated undergoing “first line therapy with Erlotinib” and smoking cessation (with varenicicline). Response to therapy was evaluated by CT scan. Data concerning clinical history, smoking habit, nicotine dependence were collected after three months from the beginning of the recruitment. Pulmonary function tests including spirometry with pletismographic technique and exhaled carbon monoxide (CO) were performed with recording of resistances, flows, volumes. A group of ten current smokers affected by NSCLC with EGFR activating mutation and concurrent mild COPD undergoing anti-EGFR treatment without smoking cessation was used to compare clinical and functional data. A control group of NSCLC wild type with mild COPD undergoing smoking cessation was assessed for functional data. Results: Twenty-five patients were enrolled. All of them reported partial response at CT re-evaluation. All functional indexes and parameters were improved after combined treatment a significant increase of FEV1 level and a decrease of exhaled CO. In particular, a mean increase of FEV1 from 1.93 (SD 0.48) to 2.03(SD 0.46) liters was recorded. A notable reduction of sRAW (specific resistances) was also observed. The improvement of some parameters such as CO, heart rate (HR), sRAW and FEV1 resulted statistically significant. A better response to therapy was found “in the study group compared to the second group of mutated NSCLC patients”. In this second group, we also observed an improvement of functional obstructive parameters although it was less remarkable than study group. Only sRAW and FEF 25/75 were significantly increased. The group of NSCLC wild type undergoing only smoking cessation showed a lower increase of FEV1 by about 50 ml compared to the first group. Conclusion: The combination of anti-EGFR treatment and concurrent therapy for smoking cessation seems to be more effective than erlotinib alone in improving lung function and clinical response in advanced NSCLC patients with EGFR-mutations. It is conceivable that erlotinib may potentiate the action of varenicline. We have also outlined some relevant patents concerning varenicline and EGFR-TKI.
Keywords: EGFR mutation, erlotinib, NSCLC, smoking, spirometry, TKI, varenicline.
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