A Clinical Study Of S-1 With Concurrent Radiotherapy In Elderly Patients With Esophageal Cancer

Part ? A phase ? dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancerBackground: Concurrent chemoradiotherapy with 5-fluorouracil and cisplatin are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer.This Phase I trial was designed to determine the maximum tolerated dose and dose-limiting toxicity of S-1,an oral 5-fluorouracil derivative,when given with radiotherapy in elderly patients.Methods: Patients who were age of 70 years or older with histologically confirmed esophageal cancer,and had an Eastern Cooperative Oncology Group score of 0-2 were eligible for this study.Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy.S-1 was administered on days 1-14 and 29-42 at the following dosages: 60,70,and 80 mg/m2/day.Results: Twelve previously untreated patients were enrolled in this study.No grade 3 or 4 toxicity was observed in 6 patients treated at the 60 and 70 mg/m2 dose levels.Dose-limiting toxicity was observed in 4 of 6 patients treated at the 80 mg/m2 dose level.Two patients developed grade 3 esophagitis,1 patient developed grade 3 esophagitis and pneumonitis,and 1 patient developed grade 3 thrombocytopaenia.Endoscopic complete response was observed in 8 patients(66.7%).The median progression free survival was 20 months and median overall survival was 29 months.Conclusions: The maximum tolerated dose of S-1 was 80mg/m2,and the recommended dose for Phase ? studies was 70mg/m2.This regimen was well tolerated and active in elderly patients with esophageal cancer,meriting further investigation in phase ? studies.Part ? A phase ? study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancerBackground: Concurrent chemoradiotherapy(CCRT)using conventional platinum-based doublets are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer.We previously reported a phase I trial of CCRT using S-1,an oral 5-fluorouracil derivative,which yielded well safe and active outcomes.Against this background,we subsequently conducted a phase ? trial of this regimen.The primary end-point was overall survival,and the secondary end-points included toxicities,response rate and progression-free survival.Methods: Patients with histologically confirmed esophageal cancer,who were age of 70-85 years with Eastern Cooperative Oncology Group performance status(PS)score of 0-2 or age of 65-69 years with PS score of 2,were eligible for this study.Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy.S-1 70mg/m2/day was administered on days 1-14 and 29-42.Results: Thirty patients with esophageal cancer were enrolled in this study,including 11 patients aged 65-69 with performance status(PS)score of 2 and 19 patients aged 70-85 with PS score of 0-2.No grade 4 toxicity or treatment-related death occurred.The grade 3 toxicities included esophagitis(16.7%),leucopoenia(13.3%),neutropenia(10%),anaemia(3.3%),pneumonitis(3.3%)and fatigue(3.3%).Six and 11 patients experienced complete responses(20%)and partial responses(36.7%),respectively.Twelve patients exhibited stable disease(40%).The median progression-free survival time was19.0 months and the 2-year progression-free survival rate was 40.8%.The median survival time and the 2-year overall survival rate were 24 months and 45.1%,respectively.Conclusions: The administration of concurrent chemoradiotherapy with S-1 demonstrated favorable efficacy,with acceptable toxicity,in elderly patients with esophageal cancer.It is worth carrying out a phase ? trial to further access the clinic value of this regimen.Part ? S-1 Concurrent with radiotherapy versus radiotherapy alone for elderly Chinese patients with carcinoma of esophagus: results of an interim analysis of a prospective,randomized,multi-center phase ? studyBackground: We previously reported the phase I/? trial of concurrent chemoradiotherapy(CCRT)using S-1,an oral 5-fluorouracil derivative,which yielded well safe and active outcomes.This randomized,multi-center phase ? trial aimed to further assess the efficacy and safety of S-1 concurrent with radiotherapy versus radiotherapy alone for elderly Chinese patients with carcinoma of esophagus.Methods: Eligible patients with histologically confirmed esophageal cancer,who were age of 70 years or older were stratified by age and tumor length,randomly assigned to receive either CCRT or radiotherapy alone.The CCRT group received 54 Gy radiotherapy in 30 fractions concurrent with S-1 70mg/m2/day on days 1-14 and 29-42,and another group received 60 Gy radiotherapy in 30 fractions.The primary endpoint was 2-year survival rate.This study is registered with Clinical Trials.gov,number NCT02813967.Results: Between June 2016 and February 2018,a total of 278 patients were enrolled in this study,and 254 patients had completed the treatment.Among them,128 cases were randomly allocated to the CCRT group and 126 cases to the radiotherapy alone group.Treatment arms were well balanced with respect to baseline characteristics.Seventy six percent of patients in CCRT group recieved full dose of chemotherapy,while 88.3% and 84.9% patients recieved full dose of radiotherapy in CCRT group and radiotherapy alone group,respectively.Toxicities were mild in both groups.Treatment related deaths were not observed in the CCRT group,and 2 patients died of radiation pneumonia in the radiotherapy alone group.The complete response was achiveved in 43% and 29.3%,respectively.After a median follow-up of 6 months,18 and 26 patients died in CCRT group and radiotherapy alone group,respectively.Conclusion: This interim analysis demonstrates that S-1 concurrent with radiotherapy increase tumor responses compared with radiotherapy alone.It is needed to continue this study to assess survival.