食管癌同期放化疗PF方案剂量递增试验

Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

目的确定同期放化疗食管癌时顺铂(PDD)和氟尿嘧啶(5-Fu)方案的中国人最大耐受量(MTD)并观察其毒副反应。方法15例初治食管癌患者成为研究对象。全程常规分割照射,总剂量60 Gy分30次。同期化疗采用改良Fibonacci法,从低剂量逐渐上升到高剂量,起始剂量为PDD 37．5 mg/m^2第1天,5-Fu 500 mg/m^2第1～5天,28 d为1个周期,共4个周期。递增剂量为PDD 7．5mg/m^2,5-Fu 100mg/m^2,每剂量组至少3例,如无剂量限制毒性(DLT)出现则进入下一剂量组,直至出现DLT,DLT的次一剂量即为MTD。结果DLT为3级放射性食管炎,发生于PDD 60 mg/m^2,5-Fu 700 mg/m^2剂量水平；则其次一剂量PDD 52．5 mg/m^2,5-Fu 700 mg/m^2即为MTD。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。结论同期放化疗食管癌PF方案的中国人最大耐受量为PDD 52．5mg/m^2第1天,5-Fu 700 mg/m^2第1～5天,28 d为1个周期,共4个周期。

Objective To define the maximum-tolerated dose（MTD） and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m^2 D1 and 5-fluorouracil 500 mg/m^2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m^2 and 5- fluorouracil 100 mg/m^2. Every cohort contained at least 3 patients. If no dose-limiting toxicity（DLT） was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m^2, 5-fluorouracil 700 mg/m^2. MTD was defined as cisplatin 52.5 mg/m^2, 5- fluorouracil 700 mg/m^2. The major side effect were radiation-induced esophagitis, leueopenia, nausea, vomiting and anorexia. Colndusion Maximun tolerated dose of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy in the Chinese people with esophageal carcinoma were cisplatin 52.5 mg/m^2 D1,5-fluorouracil 700 mg/m^2 D1-5, repeated 4 times every 28 days.