Effect Of S-1 Maintenance Chemotherapy Following First-line Regimen In Patients With Advanced Esophageal Cancer

Background and purposeEsophageal cancer is a serious fatal tumor,which ranked top six around the world,especially in China [1].However,compared with Western countries and Japan,we are far behind the times and contributed minimal level A evidence[2-3].Because esophageal cancer is easy to transfer to lymph nodes and distant organs,this cancer is more malignant than other gastrointestinal cancers.Because of the serious invasion,malignant progression,and poor condition of patients,esophageal cancer is one of the most difficult cancers to treat,when it is locally advanced or widespread metastasis.Moreover,esophageal cancer can severely destroy the respiratory and nutritional system of the patients,which leads to a poor prognosis [4-5].Several clinical trials showed that the overall 5-year survival rate of patients with esophageal cancer is only 5%-30%.Esophagectomy is a very common clinical method to treat esophageal cancer,which is considered as a pivotal treatment for early-stage and localized esophageal cancer.However,esophagectomy shows less effect on elderly patients,especially on terminal-stage patients[6-8],most patients are too late to have a surgery as soon as diagnosed that they have to rely on chemotherapy [9].According to previous 10 to 15 years study,clinical trials have demonstrated that combination of some therapy and surgery could improve survival rate of esophageal patients[10-11].Therefore,chemotherapy plays an important role in patients with metastatic disease.The combination of cisplatin and 5-fluorouracil(5-FU)is considered the firstline standard regimen.This regimen has demonstrated an overall response rate of 25% to 45%[12-16],with a median survival of less than 1 year[17-19].Unfortunately,patients experience recurrence or disease progression with standard chemotherapy.Therefore,it is important to establish second-line chemotherapy regimens after failure of the standard cisplatin and 5-FU chemotherapy [20-22].But studies have found that the effectiveness of second-line chemotherapy was far less than the first-line chemotherapy.How can extend the progression-free time after chemotherapy? We used to take "Watch and wait" mode as follow-up treatment for patients who benefited from chemotherapy in the past.However recently years,drawing blood tumor successful treatment modalities[9],high efficiency and low degree of toxicity maintenance therapy has been widely accepted for other cancers such as advanced non-squamous non small cell lung cancer,ovarian cancer,gastric cancer,pancreatic cancer and colorectal cancer,The results showed that maintenance therapy could prolong progression-free survival and overall survival[23-24].But the application of single-agent maintenance therapy of esophageal cancer patients is rare.Capecitabine is an oral fluorouracil drug[25-27].A trail showed that the maintenance therapy of capecitabine for patients with inoperable esophageal cancer is more effective,and lower toxicity,the patients could tolerate the side effects[28].Tegafur,fimeracial,and oteracil are three derivatives of 5-FU,which are 5-FU pro-drug,a dihydropyrimidine dehydrogenase inhibitor,and a antidote of 5-FU,respectively.S-1 consists of the above three drugs at a molar ratio of 1:0.4:1 [29-31].Therefore,from the entire recipe structure,S-1 enhanced tumor effect,extend the duration of action,but also reduce the gastrointestinal toxicity[32-33].So far,S-1 has been successfully used in treatment of some tumors,including head and neck cancer,lung cancer and pancreatic cancer[34-36].Meanwhile,the combination chemotherapy(S-1 and cisplatin)has its own standard chemotherapeutic regimen in clinic for patients with gastric cancer[37-39].The maintenance therapy with S-1 for pancreatic cancer,gastric cancer,colorectal cancer and other gastrointestinal cancer have been reported so far[40-41].Thus we propose that S-1 could be a potential chemotherapeutic agent for the treatment of esophageal cancers.The aim of this study is to investigate the efficacy and safety of S-1 maintenance chemotherapy following first-line regimen in patients with advanced esophageal cancer.Data and MethodFrom January 2012 to December 2015,66 patients with pathologically confirmed advanced esophageal cancer without disease progression after 4 to 6 cycles of platinum-based first-line regimen chemotherapy were divided into S-1 maintenance versus observation randomly.31 patients in the maintenance group received maintenance chemotherapy with S-1(80,100 or 120 mg orally in two divided doses.The dose of S-1 was assigned on the basis of body surface area.Twice daily for 4 weeks;6 weeks for a treatment cycle until disease progression or with intolerant toxicity,and 35 patients in the control group received optimal supportive care.Clinical efficacy and adverse reactions were observed.Statistical MethodAll data are analyzed statistically by SPSS17.0 statistical software,categorical data are analyzed by chi-square test,Kaplan-Meier method was used for survival analysis.P <0.05 was considered statistically significant.ResultsAccording to the Response Evaluation Criteria in Solid Tumors(RECIST)standard,all the patients can be evaluated for therapeutic effects include complete response(CR),partial response(PR)rate and stable disease(SD).The response rate(CR+PR)was 22.6% in the maintenance group,significantly higher than that in the control group(2.9%,P <0.05).The disease control rate(CR+PR+SD)in the maintenance group was 38.7%,while the control group was 22.9%,there was no significant difference between the two groups(P>0.05).The median progressionfree survival time was 17.0 months in the maintenance group and 10.0 months in the control group(P<0.05).The most common adverse effect in the maintenance group included nausea,vomiting,leucocytopenia,and hand-foot syndrome.No death occurred in relation to the therapy.ConclusionS-1 maintenance chemotherapy,with a tolerable toxicity profile,can improve the response rate and median progression-free survival in advanced esophageal cancer patients who respond to first-line regimen.