Ⅱ/Ⅲ期直肠癌术后奥沙利铂联合5-FU同步放化疗的疗效  

Therapeutic effect of postoperative radiotherapy in combination with oxaliplatin and 5-Fu in patients with stage Ⅱ/Ⅲ rectal cancer

作　　者：李永恒 李小凡 李金銮[3] 朱向高[4] 徐博 蔡勇 

机构地区：[1]北京大学肿瘤医院 [2]北京市肿瘤防治研究所放疗科恶性肿瘤发病机制及转化研究教育部重点实验室,北京市100142 [3]福建省肿瘤医院放疗科,福建省福州市350014 [4]北京大学人民医院放疗科,北京市100044

出　　处：《世界华人消化杂志》2013年第8期729-733,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨Ⅱ/Ⅲ期直肠癌患者根治术后同步放化疗,奥沙利铂联合5-FU每周方案中奥沙利铂剂量的限制性不良反应(dose-limiting toxicity,DLT)、最大耐受剂量(maximal tolerance dose,MTD).方法:2005-02/2010-01选年龄为18-70岁、KPS评分≥70分、根治性手术后病理证实为Ⅱ/Ⅲ期的直肠癌患者入组.进行盆腔三维适形或调强放疗5wk,50Gy,共25次.每周放射治疗的第1天开始给予奥沙利铂联合5-FU(氟尿嘧啶)方案化疗,5-FU和LV(亚叶酸钙)的剂量固定分别为600mg/m2和200mg/m2,静脉滴注,奥沙利铂从40mg/m2开始递增,1次/wk,共化疗5wk.奥沙利铂DLT(剂量限制性不良反应)的定义为4级血液学毒性(除血小板减少为3级)或≥3级非血液学毒性(除外脱发).结果:9例患者分别入奥沙利铂每周40mg/m2组(3例)、50mg/m2组(3例)、60mg/m2组(3例);40mg/m2组、50mg/m2组未出现Ⅱ度以上不良反应,60mg/m2组相继出现2例DLT(3度乏力和3度腹泻各1例),Ⅰ期研究终止,继续14例患者入奥沙利铂50mg/m2组,所有患者均如期完成放化疗;50mg/m2组患者Ⅱ度骨髓抑制16.7%(3/18),Ⅰ度骨髓抑制22.2%(4/18);Ⅱ度腹泻16.7%(3/18),Ⅰ度腹泻50%(9/18),Ⅰ度恶心33.3%(6/18),Ⅰ度乏力16.7%(3/18);未出现Ⅱ度以上的不良反应;3年和5年生存率(OS)分别为86.1%和63.3%.5年无进展生存率(progression free survival,PFS)、局部复发率和远处转移率分别为56.9%、8.5%和22.3%.结论:Ⅱ/Ⅲ期直肠癌根治术后奥沙利铂联合5-FU每周方案同步放化疗是安全、可行的;奥沙利铂的最大耐受剂量为60mg/m2/wk,推荐剂量为50mg/m2/wk.AIM： To evaluate the dose limited toxicity （DLT）, maximal tolerated dose （MTD） and recommend- ed dose （RD） of oxaliplatin weekly administered with 5FU/leucovorin in combination with con- current postoperative radiotherapy in patients with stage Ⅱ/Ⅲ rectal cancer. METHODS： Patients with stage Ⅱ/Ⅲ rectal cancer after radical excision were enrolled. A modified 3＋3 dose-escalation design was usedfor evaluating 3 dose levels （40 mg/m2, 50 mg/ m2 and 60 mg/m2） of oxaliplatin and fixed-dose 5-FU/leucovorin given once weekly, with 50 Gy XRT delivered in 25 fractions of 2 Gy, five times per week over 5 weeks. Patients received oxali- platin at the assigned dose level, and 5-FU and leucovorin doses were fixed at 600 mg/m2 and 200 mg/m2 for all cohorts, respectively. Dose- limiting toxicity （DLT） was defined as any grade 4 hematologic toxicity （including grade 3 throm- bocytopenia） or grade 3 non-hematologic toxic- ity （except for alopecia）. RESULTS： Nine evaluable patients were en- rolled, including 3 treated at 40 mg/m2, 3 at 50 mg/m2 and 3 at 60 mg/m2. At dose level 3, 2 of 3 patients experienced dose-limiting diar- rhea and hypodynamia. Another 14 patients received the dose of 50 mg/m2 in a phase 2 study. Main toxicities were hematologic, pri- marily affecting neutrophils and platelets. The most common non-hematologic toxicities were gastrointestinal. None experienced grade 3 or 4 acute toxicities. The 3- and 5-year overall sur- vival （OS） rates were 86.1% and 63.3%, respec- tively. The rates of 5-year progression-free sur- vival, local failure and metastasis were 56.9%, 8.5% and 22.3%, respectively. CONCLUSION： The MTD and RD of oxaliplatin are 60 mg/m2 and 50 mg/m2, respectively. The DLT includes diarrhea and hypodynamia. The combination of oxaliplatin and 5-Fu weekly with postoperative radiotherapy was well tolerated and demonstrated encouraging efficacy in pa- tients with stage Ⅱ/Ⅲ rectal cancer after radical excision.

关 键 词：直肠癌 奥沙利铂 同步放化疗 

分 类 号：R735.37[医药卫生—肿瘤]