{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:50:09Z","timestamp":1773730209991,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T00:00:00Z","timestamp":1512345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%\u201350%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%\u201389%) and sphincter-sparing surgery (SSS): 56% (95% CI: 38%\u201374%). Common grade &amp;gt;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%\u201393%) and 94% (95% CI: 77%\u201398%), respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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%\u201378% grade 3\/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2017-0474","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T14:55:26Z","timestamp":1511189726000},"page":"2-e5","source":"Crossref","is-referenced-by-count":15,"title":["Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer"],"prefix":"10.1093","volume":"23","author":[{"given":"Emilio P.","family":"Araujo-Mino","sequence":"first","affiliation":[{"name":"Kymera Independent Physicians, Roswell, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehuda Z.","family":"Patt","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Murray-Krezan","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua A.","family":"Hanson","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranshu","family":"Bansal","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben J.","family":"Liem","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwani","family":"Rajput","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Houman","family":"Fekrazad","sequence":"additional","affiliation":[{"name":"City of Hope Cancer Center, Duarte, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenory","family":"Heywood","sequence":"additional","affiliation":[{"name":"University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fa Chyi","family":"Lee","sequence":"additional","affiliation":[{"name":"Santa Clara Valley Medical Center, San Jose, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,4]]},"reference":[{"key":"2021122509422136000_onco12294-bib-0001","author":"National Cancer Institute. Cancer Topics: Colon and Rectal Cancer","year":"2014"},{"key":"2021122509422136000_onco12294-bib-0002","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/cncr.28509","article-title":"Annual report to the nation on the status of cancer, 1975\u20132010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer","volume":"120","author":"Edwards","year":"2014","journal-title":"Cancer"},{"key":"2021122509422136000_onco12294-bib-0003","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nrclinonc.2011.118","article-title":"The current landscape of locally advanced rectal cancer","volume":"8","author":"Aklilu","year":"2011","journal-title":"Nat Rev Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0004","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1200\/JCO.2011.40.1836","article-title":"Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Results of the German CAO\/ARO\/AIO-94 randomized phase III trial after a median follow-up of 11 years","volume":"30","author":"Sauer","year":"2012","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0005","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1200\/JCO.2014.55.2281","article-title":"Milestones in the use of combined-modality radiation therapy and chemotherapy","volume":"32","author":"Lawrence","year":"2014","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0006","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1200\/JCO.1999.17.8.2396","article-title":"Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: The Lyon R90-01 randomized trial","volume":"17","author":"Francois","year":"1999","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0007","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJMoa040694","article-title":"Preoperative versus postoperative chemoradiotherapy for rectal cancer","volume":"351","author":"Sauer","year":"2004","journal-title":"N Engl J Med"},{"key":"2021122509422136000_onco12294-bib-0008","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/S0360-3016(02)02764-5","article-title":"Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients","volume":"53","author":"Valentini","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2021122509422136000_onco12294-bib-0009","doi-asserted-by":"crossref","first-page":"311","DOI":"10.4251\/wjgo.v2.i8.311","article-title":"Capecitabine for locally advanced and metastatic colorectal cancer: A review","volume":"2","author":"Koukourakis","year":"2010","journal-title":"World J Gastrointest Oncol"},{"key":"2021122509422136000_onco12294-bib-0010","doi-asserted-by":"crossref","first-page":"917941","DOI":"10.1155\/2011\/917941","article-title":"Radiation proctitis: Current strategies in management","volume":"2011","author":"Do","year":"2011","journal-title":"Gastroenterol Res Pract"},{"key":"2021122509422136000_onco12294-bib-0011","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3748\/wjg.v9.i6.1237","article-title":"Cyclooxygenase-2 expression and angiogenesis in colorectal cancer","volume":"9","author":"Xiong","year":"2003","journal-title":"World J Gastroenterol"},{"key":"2021122509422136000_onco12294-bib-0012","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S0016-5085(03)01061-8","article-title":"The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases","volume":"125","author":"Fenwick","year":"2003","journal-title":"Gastroenterology"},{"key":"2021122509422136000_onco12294-bib-0013","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1172\/JCI119400","article-title":"Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2","volume":"99","author":"Sheng","year":"1997","journal-title":"J Clin Invest"},{"key":"2021122509422136000_onco12294-bib-0014","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1200\/JCO.2003.10.045","article-title":"Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer with high-dose radiation and oxaliplatin-containing regimen: The Lyon R0-04 phase II trial","volume":"21","author":"G\u00e9rard","year":"2003","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0015","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0360-3016(02)02933-4","article-title":"Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: A phase II IATTGI study","volume":"54","author":"Carraro","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2021122509422136000_onco12294-bib-0016","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1200\/JCO.2013.53.7753","article-title":"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","volume":"32","author":"O'Connell","year":"2014","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0017","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1200\/JCO.2010.34.4911","article-title":"Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: Pathologic results of the STAR-01 randomized phase III trial","volume":"29","author":"Aschele","year":"2011","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0018","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1200\/JCO.2012.42.8771","article-title":"Clinical outcome of the ACCORD 12\/0405 PRODIGE 2 randomized trial in rectal cancer","volume":"30","author":"G\u00e9rard","year":"2012","journal-title":"J Clin Oncol"},{"key":"2021122509422136000_onco12294-bib-0019","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.radonc.2009.08.006","article-title":"Double blind randomized phase II study with radiation+5-fluorouracil+\/-celecoxib for resectable rectal cancer","volume":"93","author":"Debucquoy","year":"2009","journal-title":"Radiother Oncol"},{"key":"2021122509422136000_onco12294-bib-0020","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1161\/CIRCULATIONAHA.105.602425","article-title":"Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction","volume":"113","author":"Andersohn","year":"2006","journal-title":"Circulation"},{"key":"2021122509422136000_onco12294-bib-0021","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1056\/NEJMoa050493","article-title":"Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial","volume":"352","author":"Bresalier","year":"2005","journal-title":"N Engl J Med"},{"key":"2021122509422136000_onco12294-bib-0022","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1093\/annonc\/mdr400","article-title":"Celecoxib can prevent capecitabine-related hand-foot syndrome in stage II and III colorectal cancer patients: Result of a single-center, prospective randomized phase III trial","volume":"23","author":"Zhang","year":"2012","journal-title":"Ann Oncol"},{"key":"2021122509422136000_onco12294-bib-0023","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1093\/jnci\/djg058","article-title":"Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: A rational advance?","volume":"95","author":"Choy","year":"2003","journal-title":"J Natl Cancer Inst"},{"key":"2021122509422136000_onco12294-bib-0024","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1093\/carcin\/bgs367","article-title":"Selective Cox-2 inhibitor celecoxib induces epithelial-mesenchymal transition in human lung cancer cells via activating MEK-ERK signaling","volume":"34","author":"Wang","year":"2013","journal-title":"Carcinogenesis"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2017-0474","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2017-0474","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/23\/1\/2\/41914536\/oncolo_23_1_2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/23\/1\/2\/41914536\/oncolo_23_1_2.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T09:42:41Z","timestamp":1640425361000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/23\/1\/2\/6438719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,4]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12,4]]},"published-print":{"date-parts":[[2018,1,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2017-0474","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,1,1]]},"published":{"date-parts":[[2017,12,4]]}}}