The Impact Of The Distribution Of Gefitinib In The Pleural Fluid On The Drug Efficacy And Safety In Patients With Advanced NSCLC

Background: Gefitinib is an oral epidermal growth factor receptor tyrosine kinaseinhibitor(EGFR-TKI) which was first approved for the clinical treatment of advancednon-small cell lung cancer. The pleural space penetration and exposure of gefitinib ispoorly understood. Thus, we investigated the distribution of gefitinib innon-small-cell lung cancer (NSCLC) of malignant pleural effusion.Objective：1.To determine the concentration of gefitinib in the plasma and pleuralfluid of patients with advanced NSCLC;2.To investigate the impact of thedistribution of gefitinib in the pleural fluid on the drug efficacy and safety in patientswith advanced NSCLC of pleural effusion.Patients and Methods: We analyzed the concentration of gefitinib in plasma andpleural fluid on day1,day8and day28(4hours after administration) after beginninggefitinib therapy in10patients of advanced NSCLC with malignant pleural effusion.LC-MS/MS was used to detect the concentration of gefitinib in the plasma and pleuralfluid.Results: The mean plasma concentration of gefitinib on day1after administration was109.9ng/ml,on day8was204.4ng/ml,on day28was198.3ng/ml. The mean pleuralfluid concentration of gefitinib on day1after administration was64.1ng/ml,on day8was255.4ng/ml,on day28was255.5ng/ml. The average permeability of gefitinibfrom plasma to pleural fluid on day1was56.1%,on day8was128.8%,on day28was133.1%During the treatment,adverse effects such as diarrhea, rash, nausea,vomiting, fatigue,anorexia, headache, anemia, elevated transaminase were observed,each drug-related adverse effects was grade1-2; grade3/4adverse effects were notobserved,and patients with interstitial pneumonia was not observed too.Conclusions:1.There seems to be a significant accumulation of gefitinib in malignant pleuraleffusion with repeated dosing; 2.The patients’plasma concentration of gefitinib was not significantly affected bythe the accumulation of gefitinib in the pleural cavity;3.The drug accumulation in the pleural cavity did not increase the side effects ofgefitinib;4. Gefitinib therapy is safe and effective to the patients with advanced NSCLC ofpleural effusion.The result of our research is still required large sample clinical trials to be furtherconfirmed.