Chai Dongye,Zhang Fang

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract Objective To provide theoretical basis for clinical treatment of patients with terminal non-small cell lung cancer through the analysis of the cost and adverse reactions of the joint treatment of icotinib and pemetrexed combined with cisplatin.Methods The clinical data of the patients diagnosed with terminal non-small cell lung cancer were collected and analyzed according to different drug administration schedules (n=53 of each group).The efficacy,cost and adverse reactions were evaluated respectively,aiming to provide the pharmacoeconomic evidence for the clinical applications.Results and Conclusion There was no significant difference between the efficacy of the icotinib group and the pemetrexed combined with cisplatin group,but the cost of the icotinib group was much lower,and the adverse reactions such as leukopenia,anemia,vomiting and nausea were far fewer than those in the pemetrexed combined cisplatin group.Although the two methods have similar therapeutic effects,the icotinib group has lower cost and fewer adverse reactions.Thus,from the perspective of pharmacoeconomics,icotinib has its advantage over the traditional regimen on the treatment of terminal non-small cell lung cancer.

Keywords: non-small cell lung cancer (NSCLC);icotinib;pemetrexed;cisplatin

Lung cancer causes the highest rate of death among all malignant cancers worldwide.According to the latest report of the World Health Organization,in 2018 alone,more than 18 million new cases of cancer occurred globally,with a mortality rate of 50%.The report also showed that the prevalence of lung cancer was 36.6% in 2018,resulting in more than 1.8 million deaths,accounting for 18.4% of cancer deaths,which means that an average of 5 000 people die of lung cancer every day in the world[1].Small cell lung cancers (SCLC)and non-small cell lung cancer(NSCLC)[2]represents two histological subtypes of lung cancer.NSCLC can further be classified into squamous cell carcinoma,adenocarcinoma,large cell lung cancer,etc.More than 80% of patients with lung cancer are diagnosed with NSCLC.The main treatment for NSCLC is surgical resection combined with chemotherapy drugs for postoperative maintenance.Since most patients with NSCLC are diagnosed at the advanced stage of the cancer,only drugs can be used to extend their survival time[3].The clinical treatment strategies for patients with advanced NSCLC include chemotherapy and molecular targeted therapy[4].As to the chemotherapy regimen,pemetrexed in combination with cisplatin has achieved good results and is recommended by the National Comprehensive Cancer Network (NCCN)clinical guidelines as the first-line chemotherapy regimen for advanced non-squamous NSCLC.However,clinical data show that although such chemotherapy regimens can prolong the survival of patients,the recurrence rate is still high and the patient's tolerance is poor[5].The main targets of molecular targeted therapy for NSCLC are epidermal growth factor receptor (EGFR)and anaplastic lymphoma kinase (ALK)[6].The EGFR gene is one of the most studied and well-recognized molecular targets in lung cancer at present.The EGFR gene-targeted therapeutic approach has been gradually used in various stages of advanced NSCLC[7].

Currently,the similar drugs that have been successfully developed internationally and clinically prescribed include icotinib,gefitinib and erlotinib.Icotinib,which was independently developed by China,is an EGFR-targeted drug for lung cancer.From preclinical studies to phase I,phase II and phase III clinical studies,it shows good safety,tolerability and efficacy,and was approved to the market 2011[8].In addition,the data of clinical trials show that the efficacy is equivalent but safer than the products on the market abroad[9].Although the clinical research and marketing time of icotinib hydrochloride is short,its efficacy and tolerance has made it a new choice for the treatment of advanced NSCLC.

Although targeted therapy for advanced lung cancer can prolong the life of patients,it also brings heavy economic pressure for many of them.This urges clinicians and researchers to use pharmacoeconomic evaluation methods to actively seek low-cost and effective treatments.Therefore,this study mainly analyzes the minimum cost of icotinib compared with traditional chemotherapy (cisplatin+pemetrexed)from the perspective of pharmacoeconomics,and evaluates the incidence of various drug-related adverse reactions.Based on the studies of the efficacy and economics of this kind of drugs in the treatment of NSCLC,a reference can be provided for clinicians to choose drugs in the future.

1 Materials and methods

1.1 Study design

This program was designed according to a single blind,random,and controlled method.

1.2 Subject

A total of 106 patients with advanced NSCLC diagnosed by pathology were enrolled.The Zubrod-ECOG-WHO score was ≤ 2,the survival time was expected to be more than 10 months,and drug allergy,abnormal liver and kidney function were excluded.

1.3 Treatment

Pemetrexed in combination with cisplatin group(control group):intravenous infusion of pemetrexed 500 mg/m2,followed by intravenous infusion of cisplatin 75 mg/m2,divided into 1-3 days,21 days per cycle,administration for 4 cycles,followed by intravenous infusion of pemetrexed for 8 cycles.Icotinib group (study group):icotinib 125 mg,orally,three times a day for 10 months.After treatment,the treatment effect and adverse reactions of the two groups were collected.All the selected patients were given conventional treatments such as gastric mucosa protection,fluid replacement and antiemetic before chemotherapy.

1.4 Evaluation criteria for efficacy and adverse reaction

The solid tumor efficacy evaluation criteria(RECIST)were used to evaluate the patient's treatment effect:complete remission (CR),partial remission (PR),stable (SD)and disease progression(PD).The calculation formula:Efficiency (RR)=(CR+PR)/ total number of cases × 100%.CRmeans that the tumor completely disappears,and it has been maintained for more than 4 weeks.PR means that the tumor length is reduced by more than 30% compared with the previous treatment,and also the status has been maintained for more than 4 weeks.SDmeans that the length of the tumor shows a shrinking trend,but it does not reach thePRlevel or it may have increased but still does not reach thePDlevel.RR represents that the total length of tumor increases by 20%,or new lesions appears.

1.5 Cost determination

In order to facilitate observation and comparison,this study only examined the direct cost:drug cost (Cdrug),genetic testing cost,nursing cost(Cnursing),and adverse reaction cost (Cadverse reaction).Because of the different drug regime,the cost calculation method was different.The formula was:C(pemetrexed combined with cisplatin)=C(drug cost)+C(nursing fee)+C(adverse reaction);C(icotinib)=C(drug cost)+C(gene detection)+C(adverse reaction).Hypothesis:Based on the fact that the average hospitalization period for severe adverse reactions was 6 days and the occurrence of more serious adverse reactions (such as vomiting,rash,diarrhea,etc.),the average cost per treatment was assumed to be 200 yuan.The specification of icotinib hydrochloride (Zhejiang Beida Pharmaceutical Co.,Ltd.)was 125 mg per tablet,21 tablets/box,and the price was 1 345.08 yuan.The specification of pemetrexe (Jiangsu Hansoh Pharmaceutical)is 200 mg/bottle,the price is 1 879.9 yuan.The specification of cisplatin injection (Jiangsu Hansoh Pharmaceutical)was 30 mg/piece,and the price is 25.22 yuan.According to a survey of hospitals in various provinces and cities,the genetic testing cost of NSCLC was about 5 000 yuan[10].

1.6 Statistical analysis

Statistical data were collected with SPSS 17.0 statistical software.The data were analyzed byχ2test.P＜ 0.05 was statistically significant.

2 Results

2.1 Basic characteristics of patients

There were no significant differences in gender,age,tumor stage and body surface area (P＞ 0.05)between the 2 groups of patients,which meant that they had comparability (See Table 1).

Table 1 General comparisons between the 2 groups

2.2 Comparison of treatment effects

There was no death among the patients during the treatment.The results showed that,after treatment,19% of the patients in the control group had complete remission,47% had partial remission,23% had stable symptoms,and 11% had progression,with a total effective rate of 66%.Compared with the control group,the total effective rate of the study group was 68%,showing that 26% of patients had complete remission,42% had partial remission,and 17% had stable symptoms,while 15% had lesion progression.There was no significant difference in the efficiency between the two groups (P＞ 0.05),as shown in Table 2.

2.3 Comparison of adverse reactions

After treatment,the adverse reactions of the two groups were compared.In the study group,there were 8 cases of fatigue (15%),10 cases of liver function reduction (19%),18 cases of rash (34%),and 8 cases of diarrhea (15%).The adverse reactions in the control group were 30 cases of leukopenia (57%),15 cases of anemia (28%),32 cases of nausea and vomiting(60%),8 cases of diarrhea (15%),and 9 cases of constipation (17%).The incidence of adverse reactions such as leukopenia,anemia,thrombocytopenia,nausea and vomiting,and constipation was much lower in the study group than in the control group,but the incidence of rash was higher in the study group.The difference between the two groups was statistically significant (P＜ 0.05),see Table 3.

Table 2 Comparison of treatment response rates between the two groups

2.4 Minimal cost analysis of the study group and the control group

The data showed that there was no significant difference in efficacy between the icotinib group and the pemetrexed plus cisplatin group in the treatment of advanced NSCLC (P＞ 0.05).Thus only the cost difference between the two groups was compared to select the better one.The total cost of the pemetrexed plus cisplatin group (control group)was 91 735.1 yuan,and the total cost of the icotinib group (study group)was 62 876.6 yuan.The results showed that the cost of icotinib treatment was much lower than that of pemetrexed plus cisplatin,and they were statistically different.Therefore,the icotinib group was the preferred treatment.

Table 3 Comparison of adverse reaction rates between the two groups

3 Discussions

The pharmacoeconomic approach is a scientific method to select the optimal treatment regimen by the comprehensive comparison of drugs' efficacy and safety.Economic principles are applied to the approach.The results of this study fully demonstrated that there was no statistical difference between icotinib and pemetrexed combined with cisplatin in NSCLC treatment.From the comparison of the incidence of adverse reactions,we could see that,except for the lower rate of rash occurrence,the incidence of adverse reactions such as leukopenia,anemia,thrombocytopenia,nausea and vomiting and constipation in the group of pemetrexed in combination with cisplatin was much higher than that of icotinib group.By calculating the medication cost of the two regimens,the total cost of the pemetrexed plus cisplatin regimen was 91 735.1 yuan,which was much higher than the the icotinib regimen with 62 876.6 yuan.From a pharmacoeconomic perspective,the ictotinib regimen (study group)was superior to the pemetrexed plus cisplatin regimen (control group).

Based on the above results,this study found that,in the treatment of advanced NSCLC,icotinib regimen was superior to pemetrexed combined with cisplatin.Although the effects of these two regimens were similar,the cost of icotinib regimen was lower.In addition,the incidence of adverse reactions such as leukopenia reduction,anemia,platelets reduction,nausea,vomiting and constipation was lower in the icotinib group than that of pemetrexed combined with cisplatin regimen.Thus,compared with the later regimen,the icotinib regimen was more suitable for the treatment of advanced NSCLC.However,due to the small number of cases collected,this study had limitations to a certain extent.The compliance,longterm survival rate,and life quality of patients were not taken into the analysis in the study.Because some cost factors were not fully controlled,there would be some limitations in this study,and further research is required.