局部不可手术切除或复发直肠癌放疗同步羟基喜树碱I期临床研究  

Phase I clinical study of concurrent chemoradiation with hydroxycamptothecin for unresectable or locally relapsed rectal cancer

作　　者：李宁[1] 金晶[1] 李晔雄[1] 王维虎[1] 王淑莲[1] 刘跃平[1] 宋永文[1] 任骅[1] 房辉[1] 刘新帆[1] 余子豪[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所放疗科,北京100021

出　　处：《中华放射肿瘤学杂志》2012年第4期348-351,共4页Chinese Journal of Radiation Oncology

摘　　要：目的探讨局部不可手术或局部复发直肠癌常规3个野等中心照射或三维适形放疗同步羟基喜树碱的剂量限制性不良反应（DLT）和最大耐受剂量。方法2004--2007年间22例局部不可手术或局部复发直肠癌患者入组研究。按照羟基喜树碱（HCPT）用法分为1次／周用药组和2次／周用药组，剂量分别为6、8、10mg／m2和4、6、8、10mg／m2，从放疗开始同步经静脉注射。盆腔常规分割，总剂量50Gy，局部肿瘤部位序贯加量10～16Gy。≥3级非血液学和4级血液学不良反应为HCPT的DLT。结果2次／周用药组8例患者完成了2个水平剂量递增试验，其中4mg／m2组未出现DLT，6mg／m2组前3例出现1例DLT（3级腹泻）、追加3例后再次出现1例DLT（3级腹泻）。1次／周用药组14例患者完成了3个水平剂量递增试验，其中6mg／m2组未出现DLT，8mg／m2组前3例出现1例DLT（3级腹泻、放射性皮炎）、追加3例后未出现DLT，10mg／m2出现1例DLT（3级腹泻）、追加的第2例出现DLT（3级恶心）。全组5年总生存率为23％，中位生存期18个月。结论局部不可手术或局部复发直肠癌放疗同步HCPT推荐每周8mg／m2，可1次或分为2次给与。剂量限制性不良反应为3级腹泻、恶心和放射性皮炎。Objective To determine the maximal tolerated dose and the dose-limiting toxicity of hydroxycamptothecin （HCPT） concurrently combined with three-dimensional conformal radiotherapy （3DCRT） for unresectable or locally relapsed rectal eancer. Methods Twenty-two patients with rectal cancer were enrolled into phase I study between 2004 -2007. HCPT was intravenously administered concurrently with 3DCRT weekly, dose given from 6,8,10 mg/m2 or twice a week, dose given from 4,6,8, 10 mg/m2 , respectively. Total radiation dose of 50 Gy was delivered to the whole pelvis at a fraction of 2 Gy per day for 5 weeks, with 10 -16 Gy subsequent boost to tumor area. Dose-limiting toxicities （DLT） were defined as grade 3 or higher non-hematologic toxicity or grade 4 hematologic toxicity. Results In the twice a week group, DLTs of grade 3 diarrhea were observed in 2 patient treated at dose of 6 mg/m2. In the weekly group, DLTs of grade 3 diarrhea and radiation-induced dermatitis were observed in 1 patient at dose of 8 mg/m2, and were not observed in the next 3 patients at the same dose level. However, at dose of 10 mg/m2, 2 patients had grade 3 diarrhea or nausea. The 5-year overall survival rate was 23% and the median survival time was 18 months. Conclusions HCPT given concurrently with 3DCRT is safe and tolerable for patients with unresectable or locally relapsed rectal cancer. Either 8 mg/m2 weekly or 4 mg/m2 twice a week can be recommended for further study. The dose-limiting toxicities are grade 3 diarrhea, nausea and radiation-induced dermatitis.

关 键 词：直肠肿瘤/同期放化疗法 放射疗法 三维适形 化学疗法 羟基喜树碱 I期临床研究 

分 类 号：R735.37[医药卫生—肿瘤]