【作者】 蔺强； 高献书； 乔学英； 周志国； 张钧； 杨香然； 万欣；

【Author】 Lin Qiang Gao Xian-Shu Qiao XueYing Zhou Zhi-Guo Zhang Jun Yang Xiang-Ran Wan Xin Department of Radiation Oncology, the fourth hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院放疗科； 北京大学第一医院放疗科；

【摘要】 目的:确定同期放化疗治疗食管癌时顺铂和5-氟尿嘧啶(PF方案)的中国人最大耐受量(MTD)并观察其毒副反应。方法:共15例初治食管癌患者成为研究对象,全程常规分割照射,每天一次,每次2．0Gy,每周5次,30分割,总剂量60Gy。处方剂量不考虑组织不均一性。GTV边界由食管X光片、CT来确定。CTV上下界为GTV上下界各外延3厘米,侧界为肿瘤侧界外延1厘米。PTV为CTV 外延1厘米。起始化疗剂量及剂量递增,参考RTGO85— 01和RTOG94-05的研究结果,初始化疗剂量选定为 DDP 37．5mg／m2,d1,快速静点,5-Fu 500mg／m2,d1-d5, 持续静点超过8小时。根据改良的Fibonacci爬坡法,从初始剂量开始,每剂量组最少3例,如无剂量限制性毒性(DLT) 出现,则升至下一剂量组,但不得在同一受试者重复试验。如该剂量组有I例出现D L T,同一剂量再做3例,如不出现D L T,可升至下一剂量组,反之则停止爬坡试验。每组间剂量递增为初始剂量的25％,即DDP 7．5mg／m2,5-Fu 100mg／ m2,前三组为两药同时递增,自第四组起改为两药交替递增。DLT定义:由于放化疗的副作用导致放疗停止大于一周,或估计威胁患者生命安全。标准:非血液学毒性:Ⅲ度或Ⅲ度以上放射性食管炎1例。II度肝肾功能、肺损伤人数大于等于本组人数1／2或出现Ⅲ度毒性。出现恶心、呕吐IV 度。厌食,乏力Ⅲ度不作为DLT。血液学毒性:在应用CSF 支持的前提下,出现WBC／ANC减少Ⅳ度,Ⅲ度白细胞减少>=7天或Ⅲ度白细胞减少性发热;Ⅲ或Ⅳ度PLT减少; Ⅲ或Ⅳ度HGB减少。DLT的次一级剂量水平即为MTD。毒性标准放疗采用RTOG／EORTC急性放射反应评分标准 1995,化疗采用NCI普通毒性标准-CTC2．0。疗前一周内完成病史、体检、KPS评分,活检病理结果,血常规、肝功能、肾功能检查,食管造影、胸部X光、胸部CT和腹部CT／ B超,心电图。结果:当剂量递增到第四剂量组,DDP60mg／ m2,5-Fu700mg／m2时,出现了2例Ⅲ三度放射性食管炎, 成为DLT,则其次一剂量DDP 52．5mg／m2,5-Fu 700mg／ m2确定为MTD。治疗主要毒副反应为放射性食管炎、白细胞减少、恶心呕吐和厌食。结论:同期放化疗治疗食管癌PF 方案的中国人最大耐受量为DDP 52．5mg／m2 d1,5-Fu 700mg／m2 d1-d5,每28天重复,共4周期。更多还原

【Abstract】 Objective: To define the maximum-tolerated dose(MTD) and observe the side effect of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy in Chinese people with esophageal carcinoma. Methods: Previously untreated fifteen patients with esophageal carcinoma received conventional fractionation radiotherapy, 5 daily fractions of 2.0Gy per week. The total radiation dose was 60Gy. Concurrent chemotherapy dose escalation was performed by modified Fibonacci sequence. The starting doses were cisplatin 37.5mg/m2 on day 1 and 5-fluorouracil 500mg/m2 on days l-5,respectively.The regimen was repeated 4 times every 28 days. Escalation doses were cisplatin 7.5mg/m2 and 5-fluorouracil 700mg/m2.Every cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for enrollment. The courses were repeated until DLT appeared. MTD was declared as one dose level below the level at which DLT appeared. Results: DLT was grade 3 radiation-induced esophagitis at the level of cisplatin 60mg/m2,5-fluorouracil 700mg/m2.MTD was defined as cisplatin 52.5mg/m2,5-fluorouracil 700mg/m2.The major side effect were radiation-induced esophagitis, leucopenia, nausea and vomiting and anorexia. Conclusion: MTD of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy in Chinese people with esophageal carcinoma were cisplatin 52.5mg/m2 on day 1,5-fluorouracil 700mg/m2 on days 1-5, repeated 4 times every 28 days.更多还原