Clinical Study Of Gefitinib Combined With Tetramethylpyrazine In The Treatment Of Advanced Lung Adenocarcinoma With EGFR Mutation

Objective:Lung cancer have the highest incidence and mortality rates in the world.About the treatment,targeted therapy has its advantages of high efficiency,low toxicity and high selectivity.However,the problem of targeted drug resistance is inevitable.Gefitinib is a targeted drug for EGFR-sensitive mutations in lung cancer.Through a large number of clinical observations and data reports,patients treated with gefitinib will develop drug resistance after about 9 months,and the disease will progress.A number of experimental data show that tetramethylpyrazine has delay the effect of anti-tumor drug resistance^[1].At present,the effect of tetramethylpyrazine on delaying drug resistance of targeted drugs has not been reported.So we conducted this study,hoping to treat the patients who have advanced lung adenocarcinoma with EGFR mutation by combining gefitinib with tetramethylpyrazine,to observe that delay the occurrence of targeted drug resistance.Methods:Patients with advanced lung adenocarcinoma with EGFR mutation who were admitted to the department of oncology,Chifeng Municipal Hospital from September 2017 to March 2019.According to the experimental design,50 patients were divided into experimental group of gefitinib combined with tetramethylpyrazine and the control group of gefitinib monotherapy.In December 2018,this project was reviewed by the ethics committee of Chifeng Municipal Hospital.In the experimental group,25 eligible patients were collected from December 2018 to March 2019.Meanwhile,60 patients with single-drug gefitinib who met the enrollment criteria from 2017.09 to 2018.12 in our hospital were collected retrospectively according to the same enrollment criteria,and 25 patients were randomly selected as the control group.The experimental group was given gefitinib 250 mg once a day,on an empty stomach or at meals,and tetramethylpyrazine 50 mg tablets,3 times a day.The control group was treated with single drug gefitinib.To evaluate the Progression Free Survival（PFS）of the two groups,and to observe whether tetramethylpyrazine can delay the occurrence of gefitinib resistance.At the same time,self-control and inter-group control were used to observe whether tetramethylpyrazine could increase tumor remission rate and improve patients’quality of life by evaluating physical condition,short-term efficacy and toxic and side effects.Results:1.In the gengral population,progression-free survival was 11.63 months in the experimental group and 8.73 months in the control group,showing a statistically significant difference（P=0.006）.2.Compared with the short-term objective efficacy,the objective remission rate（84.21%）and disease control rate（94.74%）of the experimental group were higher than those of the control group that objective remission rate（80.00%）and disease control rate（92.00%）,but the difference between the two groups was not statistically significant（P>0.05）.3.Comparison of physical strength status:（1）comparison between groups:there was no statistical difference in Performance Status score between the two groups before treatment（P>0.05）,but could be compared.After treatment,the experimental group was better than the control group,with statistically significant difference（P<0.05）.（2）Intra-group comparison:the Performance Status scores of the patients before and after treatment were improved in both the experimental group and the control group,with statistically significant differences（P<0.05）.4.The incidence and safety of adverse reactions were compared.The incidence of rash,diarrhea,nausea and vomiting and liver function damage in the experimental group was lower than that in the control group,but the difference was not statistically significant（P>0.05）.Conclusion:Patients with advanced lung adenocarcinoma treated with gefitinib combined with tetramethylpyrazine had longer progression-free survival than the control group,suggesting that combination therapy can delay the onset of gefitinib resistance.The PS score of the combined drug group was lower than that of the single drug gefitinib group,suggesting that tetramethylpyrazine can improve patients’quality of life.