局部晚期胃癌术后替吉奥同期IMRT的Ⅰ期临床研究

A phase Ⅰ study of concurrent S-1 and IMRT as adjuvant treatment for locally advanced gastric cancer after operation

目的 观察局部晚期胃癌术后替吉奥同期IMRT中,替吉奥的MTD和DLT.方法 入组标准为接受R0或R1切除、术后病理证实为TxN1～3M0期近端或远端胃腺癌患者.术后放疗采用IMRT,R0术后总剂量45 Gy分25/次5周完成,R1术后在45 Gy基础上对吻合口进行局部加量10.8Gy分6次.替吉奥剂量水平分6级,分别为Ⅰ级30 mg/（m2·d）（6例）、Ⅱ级40 mg/（m2·d）（3例）、Ⅲ级50mg/（m2 ·d）（6例）、Ⅳ级60mg/（m2 ·d）（3例）、Ⅴ级70 mg/（m2·d）（3例）和Ⅵ级80mg/（m2 ·d）（6例）,于放疗日分2次口服.结果 2010-2013年共27例患者入组,中位年龄54岁（29 ～ 65岁）,男23例.最常见1～3级不良反应是恶心（85％）、食欲下降（85％）、白细胞减少（85％）、乏力（70％）和血小板减少（52％）.3级不良反应4例中2例为白细胞减少、2例为DLT（3级恶心和食欲下降,Ⅰ级;3级血小板下降,Ⅲ级）.在最高80mg/（m2·d）水平入组6例患者均未出现DLT后研究结束.结论 局部晚期胃癌术后替吉奥同期IMRT,替吉奥的MTD为80mg/（m2·d）,于放疗日分2次口服.该剂量被推荐为以后Ⅱ、Ⅲ期研究的剂量水平.DLT为恶心、食欲下降和血小板减少.

Objective To determine the maximum tolerated dose （MTD） and dose-limiting toxicity （DLT） of tegafur,gimeracil and oteracil （S-1） which was used concurrently with intensity-modulated radiotherapy （IMRT） for locally advanced gastric cancer after operation.Methods We enrolled patients who were confirmed to have TxN1-3 M0 gastroesophageal or gastric adenocarcinoma after complete resection with a negative margin （R0） or a positive margin （R1）.IMRT was delivered at 45 Gy/25 fractions （5 fractions/week） after R0 resection or at 45 Gy with a boost dose of 10.8 Gy for anastomosis after R1 resection.S-1 was orally administered twice every day of radiotherapy at a dose of 30 mg/（m2 · d） （level Ⅰ,n =6）,40 mg/（m2 · d） （level Ⅱ,n =3）,50 mg/（m2 · d） （level Ⅲ,n =6）,60 mg/（m2 · d） （level Ⅳ,n=3）,70mg/（m2 · d）（levelⅤ,n=3）,or80mg/（m2 · d）（levelⅣ,n=6）.Results Twenty-seven patients were recruited from 2010 to 2013,with a median age of 54 years （29-65 years） and a male-to-female ratio of 23 vs.4.Grade 1-3 nausea （23 patients,85%）,anorexia （23 patients,85%）,leukopenia （23 patients,85%）,fatigue （19 patients,70%）,and thrombocytopenia （14 patients,52%） were the most common toxicities.Of four patients who developed grade 3 toxicities,two had leucopenia,and two had DLT （grade 3 nausea and anorexia in one patient at level 1 ;grade 3 thrombocytopenia in one patient at level Ⅲ）.This study ended with none of the 6 patients who received S-1 at 80 mg/（m2 · d） （level Ⅳ） developing DLT.Conclusions S-1 with concurrent IMRT is safe and tolerable for locally advanced gastric cancer patients after operation.The MTD of S-1 is 80 mg/（m2 · d）,which is recommended as the dose level in phase Ⅱ and Ⅲ studies,and S-1 is orally administered twice every day of radiotherapy.The DLT are nausea,anorexia,and thrombocytopenia.