Analysis Of The Correlation Between Clinical Curative Effect,Adverse Events And The Pharmacokinetic Characteristic Of Icotinib

Objective:This research was to observe the correlation between pharmacokinetic characteristics and the clinical curative effect of icotinib in treatment for Chinese patients with non-small cell lung cancers (NSCLC).Methods:A retrospective analysis was made on clinical data of a single center phase Ⅰ open clinical trial of icotinib at Peking Union Medical College Hospital from August2007to April2009. This research reviewed the clinical data, efficacy and pharmacokinetics of40patients in the phase Ⅰ study. Pharmacokinetic datas such as Tmax， Cmax, AUC0-∞, AUCextrap%, Vz/F, CL/F, Clast, Tlast, AUC0-last, etc were analyzed in every single patient with single dosing and continuous dosing. At last, correlation test was validated, to research the correlation between pharmacokinetic characteristics and the clinical curative effect.Results:In terms of clinical efficacy, Icotinib is better than Erlotinib and Gefitinib in PFS, OS. The median PFS in this research is160days and the median OS is454days.The results of TRUST research show that the median PFS of Erlotinib is98days, and median OS of Erlotinib is233days.The results of INTEREST research show that the median OS of Gefitinib is228days. Zhongzhen Guan etc. found that the median PFS of Gefitinib is97days, and the median OS is300days. Icotinib can improve the quality of life, and can significantly relieve lung cancer related clinical symptoms. The symptoms such as fatigue, nausea and vomiting, pain, loss of appetite, diarrhea are relieved. The reduction of pain is an important prognostic factor of patients with lung cancer. The most common adverse event is skin rashes followed by diarrhea. A main serious adverse event is interstitial lung disease. Pharmacokinetic results show that Icotinib is easily absorbed and the metabolic rate of Icotinib in patients is fast. The results of correlation analysis of the clinical efficacy and pharmacokinetic parameters show that the drug exposure (Cmax and AUC) has no significant correlation with clinical antitumor effect. This conclusion might be related with the small sample size of this study. But in smoking patients, OS seems to have correlation with AUC0-last.It is possible that smoking can affect the drug exposure. This research doesn’t find any correlation between the incidence and severity of adverse events with pharmacokinetic parameters.