雷替曲塞对比氟尿嘧啶／亚叶酸钙联合奥沙利铂治疗晚期结直肠癌的前瞻性临床研究

Raltitrexed cancer： a Department Technology, versus fluorouracil/leucovorin combined with oxaliplatin for advanced colorectal prospective study

目的前瞻性比较雷替曲塞对比氟尿嘧啶（FU）／亚叶酸钙（LV）联合奥沙利铂治疗晚期结直肠癌的疗效和安全性。方法经病理组织学和，或细胞学确诊的晚期结直肠癌患者50例，随机分组信件形式进人试验组和对照组，每组25例，各脱落1例。试验组：雷替曲塞3mg／m^2，静脉滴注≥15min，第1天；奥沙利铂130mg／m^2，静脉滴注2h，第1天。对照组：LV100mg/^2，静脉滴注2h，第1～3天；FU400mg／m^2，静脉滴注2h；紧接FU600mg／m^2，持续静脉滴注，第1—3天；奥沙利铂同试验组。两组方案均为每3周重复，每3周为1个周期。每2个周期评价疗效，直至疾病进展或不良反应不能耐受，最多用6个周期。结果试验组和对照组的有效率分别为37．50％（9／24）、33．33％（8／24），差异无统计学意义（P〉0．05）；疾病控制率分别为83．33％（20／24）和70．83％（17／24），差异无统计学意义（P〉0．05）。试验组中位无疾病进展时间11．0个月，明显优于对照组的9．0个月（95％CI8．643—11．357，P=0．015）。主要不良反应包括食欲减退、呕吐、中性粒细胞减少、红细胞减少、血小板减少、神经毒性、疲劳、转氨酶异常等，两组比较差异无统计学意义（P〉0．05）。结论雷替曲塞联合奥沙利铂方案是晚期结直肠癌有效的治疗方案，较传统的以FU为基础的联合化疗方案使用方便，减少静脉暴露时间，缩短住院时间，并且在有效率、生存期方面优于或不劣于以FU为基础的联合化疗，是值得推荐的治疗晚期结直肠癌的化疗方案。

Objective To compare the effectiveness and safety of raltitrexed and fluorouracil （FU） /leucovorin （LV） combined with oxaliplatin for advanced colorectal cancer. Methods Fifty patients with advanced colorectal cancer diagnosed by histopathology or cytology were randomly divided into two groups with 25 cases each by envelope, but 1 case lost. Patients in experimental group were treated with raltitrexed （3 mg/m^2, ≥ 15 rain intravenously） combined with oxaliplatin （130 mg/m^2 on day 1 ）, patients in control group were treated with FU/LV combined with oxaliplatin：LV 100 mg/m^2 infusion （over 2 h, from day 1 to day 3） followed by FU （400 mg/m^2 infusion in 2 h and 600 mg/m^2 continuous infusion from day 1 to day 3）, combined with oxaliplatin （ 130 mg/m^2 on day 1 ）, 3 weeks were as one cycle. Patients received 6 or less cycles until disease progressed or toxicity could not be tolerated. Results Effective rate was 37.50%（9/24） and 33.33%（8/24） in experimental group and control group respectively （P 〉 0.05）. Disease control rate in experimental group was 83.33% （20/24） while in control group was 70.83% （ 17/24 ） （P 〉 0.05 ）. The median time of progression-free survival （PFS） in experimental group and control group was 11.0 months and 9.0 months respectively （95% CI 8.643-11.357,P = 0.015）. Main adverse effects were anorexia, vomiting, neutropenia, thrombopenia, anemia, neurotoxicity, fatigue, aminotransferase abnormality, and so on. There was no statistic difference between two groups in side effects（P 〉 0.05 ）. Conclusions Rahitrexed combined with oxaliplatin is an effective regimen for the advanced colorectal cancer. Compared with traditional FU-based regimen, it is more convenient. Patients will have less venous exposure time and hospital days. Effective rate and mean survival time are superior or not inferior in rahitrexed treatment to that of FU-based regimen. Raltitrexed combined with oxaliplatin is worthy to be recommended in treating colorectal cancer.