Ji Yongling, Qiu Guoqing, Sheng Liming, Sun Xiaojiang, Zheng Yuanda, Chen Ming, Du Xianghui
1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China ; 2 Key Laboratory of Radiation Oncology, Hangzhou 310022, China ; 3 Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou 310022, China.
J Thorac Dis. 2016 Mar;8(3):451-8. doi: 10.21037/jtd.2016.02.70.
Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) 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 (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients.
Patients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) 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/m(2)/day.
NCT01175447 (ClinicalTrials.gov).
Twelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m(2) dose levels. DLT was observed in four of six patients treated at the 80 mg/m(2) dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months.
The MTD of S-1 was 80 mg/m(2), and the recommended dose (RD) for phase II studies was 70 mg/m(2). This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies.
对于老年食管癌患者，5-氟尿嘧啶（5-FU）和顺铂（CDDP）同步放化疗（CRT）常常伴随着显著的毒副作用发生率。本I期试验旨在确定老年患者放疗时口服5-FU衍生物S-1的最大耐受剂量（MTD）和剂量限制毒性（DLT）。
年龄70岁及以上、组织学确诊为食管癌且东部肿瘤协作组（ECOG）评分为0 - 2的患者符合本研究条件。放疗每周5次，每次1.8 Gy，总剂量54 Gy。S-1在第1 - 14天和第29 - 42天按以下剂量给药：60、70和80 mg/m²/天。
NCT01175447（ClinicalTrials.gov）。
12例既往未接受过治疗的患者入组本研究。在60和70 mg/m²剂量水平治疗的6例患者中未观察到3级或4级毒性反应。在80 mg/m²剂量水平治疗的6例患者中有4例观察到DLT。2例患者发生3级食管炎，1例患者发生3级食管炎和肺炎，1例患者发生3级血小板减少症。8例患者（66.7%）观察到内镜下完全缓解（CR）。无进展生存期（PFS）中位数为20个月，总生存期中位数为29个月。
S-1的MTD为80 mg/m²，II期研究的推荐剂量（RD）为70 mg/m²。该方案在老年食管癌患者中耐受性良好且有活性，值得在II期研究中进一步探究。
