O'Connell Michael J, Colangelo Linda H, Beart Robert W, Petrelli Nicholas J, Allegra Carmen J, Sharif Saima, Pitot Henry C, Shields Anthony F, Landry Jerome C, Ryan David P, Parda David S, Mohiuddin Mohammed, Arora Amit, Evans Lisa S, Bahary Nathan, Soori Gamini S, Eakle Janice, Robertson John M, Moore Dennis F, Mullane Michael R, Marchello Benjamin T, Ward Patrick J, Wozniak Timothy F, Roh Mark S, Yothers Greg, Wolmark Norman
Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital
J Clin Oncol. 2014 Jun 20;32(18):1927-34. doi: 10.1200/JCO.2013.53.7753. Epub 2014 May 5.
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 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).
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).
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.
直肠癌患者术前放疗（RT）时联合使用的最佳化疗方案尚不清楚。美国国家外科辅助乳腺和肠道项目试验R-04比较了四种与放疗联合使用的化疗方案。
临床分期为II期或III期的直肠癌患者，接受术前放疗（5周内分25次给予45 Gy，外加3至6次每日分割剂量的5.4 Gy至10.8 Gy的增量放疗），被随机分配至以下化疗方案之一：持续静脉输注氟尿嘧啶（CVI FU；225 mg/m²，每周5天），联合或不联合静脉注射奥沙利铂（50 mg/m²，每周1次，共5周），或口服卡培他滨（825 mg/m²，每日2次，每周5天），联合或不联合奥沙利铂（50 mg/m²，每周1次，共5周）。在随机分组前，外科医生根据临床分期表明患者是否适合保留括约肌手术。手术终点为完全病理缓解（pCR）、保留括约肌手术和手术降期（转换为保留括约肌手术）。
2004年9月至2010年8月，1608例患者被随机分组。在CVI FU方案与卡培他滨方案之间，以及含或不含奥沙利铂的两种方案之间，pCR率、保留括约肌手术率或手术降期率均未发现显著差异。接受奥沙利铂治疗的患者出现3级或4级腹泻的情况明显更多（P <.001）。
与CVI FU相比，术前放疗联合使用卡培他滨在pCR率、保留括约肌手术率和手术降期率方面相似。添加奥沙利铂并未改善手术结果，但增加了显著的毒性。当发生方案规定数量的事件时，将对局部肿瘤控制、无病生存期和总生存期进行最终分析。
