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Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer

LESSONS LEARNED. 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...

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Autores principales: Araujo‐Mino, Emilio P., Patt, Yehuda Z., Murray‐Krezan, Cristina, Hanson, Joshua A., Bansal, Pranshu, Liem, Ben J., Rajput, Ashwani, Fekrazad, M. Houman, Heywood, Glenory, Lee, Fa Chyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AlphaMed Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759821/
https://www.ncbi.nlm.nih.gov/pubmed/29158365
http://dx.doi.org/10.1634/theoncologist.2017-0474
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author Araujo‐Mino, Emilio P.
Patt, Yehuda Z.
Murray‐Krezan, Cristina
Hanson, Joshua A.
Bansal, Pranshu
Liem, Ben J.
Rajput, Ashwani
Fekrazad, M. Houman
Heywood, Glenory
Lee, Fa Chyi
author_facet Araujo‐Mino, Emilio P.
Patt, Yehuda Z.
Murray‐Krezan, Cristina
Hanson, Joshua A.
Bansal, Pranshu
Liem, Ben J.
Rajput, Ashwani
Fekrazad, M. Houman
Heywood, Glenory
Lee, Fa Chyi
author_sort Araujo‐Mino, Emilio P.
collection PubMed
description LESSONS LEARNED. 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. BACKGROUND. 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. METHODS. 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/m(2) b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m(2) intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions. RESULTS. 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. CONCLUSION. 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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spelling pubmed-57598212018-01-16 Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer Araujo‐Mino, Emilio P. Patt, Yehuda Z. Murray‐Krezan, Cristina Hanson, Joshua A. Bansal, Pranshu Liem, Ben J. Rajput, Ashwani Fekrazad, M. Houman Heywood, Glenory Lee, Fa Chyi Oncologist Clinical Trial Results LESSONS LEARNED. 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. BACKGROUND. 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. METHODS. 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/m(2) b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m(2) intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions. RESULTS. 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. CONCLUSION. 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. AlphaMed Press 2017-11-20 2018-01 /pmc/articles/PMC5759821/ /pubmed/29158365 http://dx.doi.org/10.1634/theoncologist.2017-0474 Text en © AlphaMed Press; the data published online to support this summary is the property of the authors
spellingShingle Clinical Trial Results
Araujo‐Mino, Emilio P.
Patt, Yehuda Z.
Murray‐Krezan, Cristina
Hanson, Joshua A.
Bansal, Pranshu
Liem, Ben J.
Rajput, Ashwani
Fekrazad, M. Houman
Heywood, Glenory
Lee, Fa Chyi
Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title_full Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title_fullStr Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title_full_unstemmed Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title_short Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer
title_sort phase ii trial using a combination of oxaliplatin, capecitabine, and celecoxib with concurrent radiation for newly diagnosed resectable rectal cancer
topic Clinical Trial Results
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759821/
https://www.ncbi.nlm.nih.gov/pubmed/29158365
http://dx.doi.org/10.1634/theoncologist.2017-0474
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