Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04
Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04
复制标题
DOI：
10.1200/jco.2013.53.7753
复制
发表时间：
2014-06-20
影响因子：
45.3
通讯作者：
Wolmark, Norman
中科院分区：
文献类型：
--
作者：
O'Connell, Michael J.;Colangelo, Linda H.;Wolmark, Norman
直肠癌患者的最佳化疗方案与术前放射治疗(RT)同时进行尚不清楚。国家外科辅助乳肠计划试验R-04对四种化疗方案与放疗同期进行了比较。患者和方法临床II或III期直肠癌患者术前放疗(45Gy25次/次，超过5周，加5.4Gy10.8Gy3~6次/天)被随机分配到以下化疗方案之一：持续静脉滴注氟尿嘧啶(CVI Fu；用或不用奥沙利铂(50 mg/m(2)，每周1次，共5周)或卡培他滨(825 mg/m(2)，2次，每日2次，每周5天)，加或不加奥沙利铂(50 mg/m(2)，每周1次，共5周)。在随机分配之前，外科医生根据临床分期指出患者是否有资格接受保括约肌手术。手术终点为完全病理反应(PCR)、保留括约肌手术和手术降级(中转为保留括约肌手术)。结果从2004年9月到2010年8月，1608例患者被随机分配。在CVI FU和卡培他滨方案之间，或者在使用或不使用奥沙利铂的两种方案之间，在PCR率、保括肌手术或手术降期率方面没有显著差异。接受奥沙利铂治疗的患者有明显更多的3级或4级腹泻(P<；.001)。结论与CVI Fu相比，接受卡培他滨联合术前RT可获得相似的PCR率、保括约肌手术和手术降期率。加入奥沙利铂并没有改善手术结果，但增加了显着的毒性。对局部肿瘤控制、无病存活率和总体存活率的最终分析将在方案规定的事件发生数发生时进行。(C)美国临床肿瘤学会2014年
The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT.Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery).Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001).Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. (C) 2014 by American Society of Clinical Oncology