一项在II期或III期直肠癌患者中开展的III期研究（NSABP R-04）表明，将术前新辅助放疗与卡培他滨或五氟尿嘧啶联合应用，其效果等同。研究结果将于2014年ASCO GI会议上公布。

卡培他滨是一种与五氟尿嘧啶相似的药物。这一试验充分证实，应用五氟尿嘧啶和卡培他滨都是可以的。研究者们还发现，在这两个方案中增加另一种化疗药物——奥沙利铂不会提高疗效，反而会增加治疗的毒性作用。

研究背景：早期直肠癌通过术前化疗、放疗、手术和术后化疗可以治愈。II期或III期可手术切除的直肠癌患者一般术前进行化疗和放疗使肿瘤缩小。某些化疗药物（包括五氟尿嘧啶、卡培他滨和奥沙利铂）起到放疗致敏剂的作用，使肿瘤对放疗更敏感。

目前只有五氟尿嘧啶有随机临床试验数据支持，可以作为直肠癌术前治疗中的放疗致敏剂。尽管没有任何数据支持卡培他滨的应用，许多医生认为卡培他滨也有这样的作用，因为卡培他滨在转移性结直肠癌的辅助治疗中非常有效。

研究详情：

在这一四分组的临床试验中，11608位患者接受放疗同时被随机分配到五氟尿嘧啶组（1477人）、五氟尿嘧啶+奥沙利铂组（2329人）、卡培他滨组（3472人）和卡培他滨+奥沙利铂组（4330人）。患者们接受其中一种治疗方式，持续5周，再经过大约1个月后行手术治疗切除肿瘤。

各治疗组间的局部病灶控制情况、无疾病生存期和总生存期没有明显差别。3年局部病灶控制率波动在87.4%-88.2%之间。外科医生可以完全切除肿瘤的病例大约占95%，这些患者中未发现微小病灶残留。2%-4%的II期直肠癌患者和4%-11%的III期直肠癌患者术后3年局部癌症复发。每个治疗组中，大约80%的患者术后5年仍然存活着。

输注五氟尿嘧啶和卡培他滨的不良反应相似。然而，同时接受奥沙利铂治疗的患者出现了明显的腹泻和疲劳。

作者观点：

主要研究作者、来自佛罗里达大学的医学教授Carmen Joseph Allegra说：医生在应用卡培他滨时，应该非常自信自己不是在进行无效的治疗。口服卡培他滨当然比输注五氟尿嘧啶方便许多。这意味着患者只需每天吃两次药片，而不是手术放置静脉留置针，然后带泵五周。尽管卡培他滨比无氟尿嘧啶价格更贵，但是我们应该考虑到，两种治疗方式总费用的差别还受放置和维护静脉留置针和泵（供输注五氟尿嘧啶时使用）的费用影响。

2014 Gastrointestinal Cancers Symposium (GICS): Abstract 390. To be presented January 18,2014.

【摘要原文】

Background: Theprimary aims were to: 1) compare capecitabine (Cape) and continuous intravenousinfusion (CVI) 5-FU combined with pelvic radiation therapy (RT) givenpreoperatively for patients (pts) with stage II or III rectal cancer; 2)determine whether the addition of oxaliplatin (Ox) would improve pt outcomes.Preliminary results focusing on pathologic complete response, sphincter-sparingsurgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: JClin Oncol 29: 2011 Ab 3503). 

Methods: Pts with clinical stage II or III rectalcancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boostof 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of fourchemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with orwithout intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2BID 5 days/wk),with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional(L-R) tumor control included L-R tumor recurrence, less than an R0 resection(complete surgical resection), and no surgery. 

Results: From July 2004 to August2010, 1608 patients were randomly assigned and 99.2% were eligible. There wereno significant differences in L-R tumor control, DFS, or OS between regimensfor either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons.The addition of Ox was associated with significantly more grade 3-4 diarrhea(p<0.0001). Analysis of the primary endpoint showed 3-yr rates of L-R tumorcontrol ranged from 87.4%-88.2%. 3-yr rates of L-R recurrence among pts whounderwent R0 resection ranged from 2-4 % for stage II pts, and from 4-11% forstage III pts. 16% of stage II and 26% of stage III pts developed distantmetastases by 5 yrs. From 84% to 97% of pts received >80% of the idealchemotherapy dose in combination with preoperative RT. 

Conclusions: CVI 5-FU ororal Cape combined with RT produced similar outcomes and toxicity profiles.Because use of oral Cape avoids the need for central venous catheters andambulatory infusion pumps, it can be considered a new standard of care in thissetting. The addition of Ox provided no improvement in outcomes but did addsignificant toxicity.