A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus

Gary W. Falk, Navtej S. Buttar, Nathan R. Foster, Katie L Allen Ziegler, Catherine J. Demars, Yvonne Romero, Norman E. Marcon, Thomas Schnell, Douglas A. Corley, Prateek Sharma, Marcia R. Cruz-Correa, Chin Hur, David E. Fleischer, Amitabh Chak, Kenneth R. Devault, David S. Weinberg, Gary Della'Zanna, Ellen Richmond, Thomas C. Smyrk, Sumithra J. MandrekarPaul J. Limburg

Research output: Contribution to journalArticle

Abstract

Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P =.10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P =.02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.

Original languageEnglish (US)
Pages (from-to)917-926
Number of pages10
JournalGastroenterology
Volume143
Issue number4
DOIs
StatePublished - Oct 2012
Externally publishedYes

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Esomeprazole
Barrett Esophagus
Dinoprostone
Aspirin
Adenocarcinoma
Placebos
Clinical Trials
Proton Pump Inhibitors
Anti-Inflammatory Agents
Biopsy

Keywords

  • Esophageal Cancer
  • Esophagus
  • Inflammation
  • NSAIDs

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Falk, G. W., Buttar, N. S., Foster, N. R., Ziegler, K. L. A., Demars, C. J., Romero, Y., ... Limburg, P. J. (2012). A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus. Gastroenterology, 143(4), 917-926. https://doi.org/10.1053/j.gastro.2012.06.044

A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus. / Falk, Gary W.; Buttar, Navtej S.; Foster, Nathan R.; Ziegler, Katie L Allen; Demars, Catherine J.; Romero, Yvonne; Marcon, Norman E.; Schnell, Thomas; Corley, Douglas A.; Sharma, Prateek; Cruz-Correa, Marcia R.; Hur, Chin; Fleischer, David E.; Chak, Amitabh; Devault, Kenneth R.; Weinberg, David S.; Della'Zanna, Gary; Richmond, Ellen; Smyrk, Thomas C.; Mandrekar, Sumithra J.; Limburg, Paul J.

In: Gastroenterology, Vol. 143, No. 4, 10.2012, p. 917-926.

Research output: Contribution to journalArticle

Falk, GW, Buttar, NS, Foster, NR, Ziegler, KLA, Demars, CJ, Romero, Y, Marcon, NE, Schnell, T, Corley, DA, Sharma, P, Cruz-Correa, MR, Hur, C, Fleischer, DE, Chak, A, Devault, KR, Weinberg, DS, Della'Zanna, G, Richmond, E, Smyrk, TC, Mandrekar, SJ & Limburg, PJ 2012, 'A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus', Gastroenterology, vol. 143, no. 4, pp. 917-926. https://doi.org/10.1053/j.gastro.2012.06.044
Falk, Gary W. ; Buttar, Navtej S. ; Foster, Nathan R. ; Ziegler, Katie L Allen ; Demars, Catherine J. ; Romero, Yvonne ; Marcon, Norman E. ; Schnell, Thomas ; Corley, Douglas A. ; Sharma, Prateek ; Cruz-Correa, Marcia R. ; Hur, Chin ; Fleischer, David E. ; Chak, Amitabh ; Devault, Kenneth R. ; Weinberg, David S. ; Della'Zanna, Gary ; Richmond, Ellen ; Smyrk, Thomas C. ; Mandrekar, Sumithra J. ; Limburg, Paul J. / A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus. In: Gastroenterology. 2012 ; Vol. 143, No. 4. pp. 917-926.
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abstract = "Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P =.10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P =.02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.",
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T1 - A combination of esomeprazole and aspirin reduces tissue concentrations of prostaglandin E2 in patients with Barrett's esophagus

AU - Falk, Gary W.

AU - Buttar, Navtej S.

AU - Foster, Nathan R.

AU - Ziegler, Katie L Allen

AU - Demars, Catherine J.

AU - Romero, Yvonne

AU - Marcon, Norman E.

AU - Schnell, Thomas

AU - Corley, Douglas A.

AU - Sharma, Prateek

AU - Cruz-Correa, Marcia R.

AU - Hur, Chin

AU - Fleischer, David E.

AU - Chak, Amitabh

AU - Devault, Kenneth R.

AU - Weinberg, David S.

AU - Della'Zanna, Gary

AU - Richmond, Ellen

AU - Smyrk, Thomas C.

AU - Mandrekar, Sumithra J.

AU - Limburg, Paul J.

PY - 2012/10

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N2 - Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P =.10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P =.02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.

AB - Background& Aims: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE2 (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE2 was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P =.10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P =.02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE2 in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.

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