Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer.
Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer.
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DOI：
10.1634/theoncologist.2017-0474
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Lee FC
中科院分区：
文献类型：
--
作者：
Araujo-Mino EP;Patt YZ;Murray-Krezan C;Hanson JA;Bansal P;Liem BJ;Rajput A;Fekrazad MH;Heywood G;Lee FC
结直肠癌表现出高水平的环氧合酶-2(COX-2)表达，这为抑制COX-2改善临床预后提供了强大的临床前理论基础。塞来昔布是一种环氧合酶-2抑制剂，我们已经证明它可以安全地与卡培他滨和奥沙利铂联合作为直肠癌放射治疗(RT)新辅助治疗的一部分。与历史数据相比，这种组合的皮肤毒性有了显著的改善。考虑到该领域已经转向单药卡培他滨，我们相信未来卡培他滨和塞来昔布的试验仍有潜力。在新辅助治疗后病理完全缓解(PCR)的直肠癌患者中，可以看到存活率提高。环氧合酶-2(COX-2)在胃肠道恶性肿瘤中表达增加，可能成为增强病理反应的靶点。一项联合放化疗和抑制COX-2的试验被用来评估PCR率、手术结果、存活率和治疗毒性。可切除(T3-4，N1-2)直肠癌在肛缘12厘米以内的患者被纳入这项II期临床试验。新辅助治疗方案为卡培他滨850 mg/m2，2次/d。奥沙利铂50 mg/m2静脉滴注，塞来昔布200 mg，2次/d，疗程5周。每日一次，同时进行25次45次的放射治疗。32名患者进入最终分析。主要终点为：31%(95%可信区间：16%-50%)。次要终点为手术降级(SD)：75%(95%可信区间：57%-89%)和保括约肌手术(SSS)：56%(95%可信区间：38%-74%)。常见的3级毒性是腹泻和肝功能异常(各占9%)。0级和1级毒性包括放射性皮炎(分别为59%和34%)和直肠炎(分别为63%和28%)。3年无瘤生存率和总生存率分别为84%(95%CI：65%~93%)和94%(95%CI：77%~98%)。塞来昔布在直肠癌患者中的化疗耐受性良好，并显示出较高的PCR、SD和SSS发生率。在新辅助化疗的基础上加用塞来昔布，皮肤毒性的改善(34%1级和无3/4级)与历史结果(43%-78%3/4级)相比似乎是一个显著的改善。
Colorectal cancers exhibit a high level of cyclooxygenase‐2 (COX‐2) expression with strong preclinical rationale for improved clinical outcomes with COX‐2 inhibition. Celecoxib is a COX‐2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer. There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single‐agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential. Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase‐2 (COX‐2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX‐2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity. Patients with resectable (T3‐4, N1‐2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m2 b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions. Thirty‐two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%–50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%–89%) and sphincter‐sparing surgery (SSS): 56% (95% CI: 38%–74%). Common grade >3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease‐free survival and overall survival (OS) were 84% (95% CI: 65%–93%) and 94% (95% CI: 77%–98%), respectively. Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%–78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.
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影响因子：
158.5
作者：
Sauer, R;Becker, H;Raab, R
通讯作者：
Raab, R
影响因子：
29.4
作者：
Fenwick, SW;Toogood, GJ;Hull, MA
通讯作者：
Hull, MA
影响因子：
50.5
作者：
Zhang, R. X.;Wu, X. J.;Chen, G.
通讯作者：
Chen, G.
影响因子：
4.7
作者：
Wang, Zi-li;Fan, Zhi-qiang;Qu, Jie-ming
通讯作者：
Qu, Jie-ming
DOI：
10.1016/s0360-3016(02)02764-5
发表时间：
2002-07-01
影响因子：
7
作者：
Valentini, V;Coco, C;Cosimelli, M
通讯作者：
Cosimelli, M