{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T17:32:49Z","timestamp":1769275969383,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06718"],"award-info":[{"award-number":["22K06718"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Vascular endothelial growth factor (VEGF)\u2010A binding to VEGF receptor (VEGFR)2 promotes tumour angiogenesis and progression. Proton pump inhibitors (PPIs) upregulate VEGF\u2010A expression in various cancers. This study examined the association between concomitant PPI use and survival outcomes in patients with advanced gastric cancer (AGC) receiving ramucirumab, a VEGFR2\u2010targeting monoclonal antibody, plus paclitaxel (PTX) or nab\u2010paclitaxel (nab\u2010PTX). The impact of PPI use on serum VEGF\u2010A concentrations was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 152 patients with AGC receiving ramucirumab plus PTX\/nab\u2010PTX as a second\u2010line therapy. Progression\u2010free survival (PFS) was compared between PPI and non\u2010PPI users. Multivariate Cox proportional hazards analysis was used to assess the prognostic factors for PFS. Serum VEGF\u2010A concentrations were measured in blood samples from 25 patients at baseline and on Day 14 following the first ramucirumab infusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median PFS was 3.7\u00a0months (95% confidence interval [CI]: 2.8\u20134.7) for PPI users and 4.7\u00a0months (95% CI: 4.0\u20135.3) for non\u2010PPI users (hazard ratio [HR]: 1.44; 95% CI: 1.01\u20132.06;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.040). Multivariate analysis, adjusted for age, the Glasgow prognostic score, total gastrectomy and massive ascites, identified PPI use as a prognostic factor for PFS (HR: 1.48; 95% CI: 1.02\u20132.14;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.038). Serum VEGF\u2010A concentrations were higher in PPI users than in non\u2010PPI users at baseline and during ramucirumab therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Concomitant PPI use was associated with shorter PFS in patients with AGC receiving ramucirumab plus PTX\/nab\u2010PTX, likely due to elevated serum VEGF\u2010A concentrations during treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70202","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:03Z","timestamp":1755071103000},"page":"3482-3488","source":"Crossref","is-referenced-by-count":1,"title":["Association of concomitant proton pump inhibitor use with worse survival outcomes in patients with advanced gastric cancer receiving ramucirumab"],"prefix":"10.1002","volume":"91","author":[{"given":"Takuya","family":"Kaneko","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-0063","authenticated-orcid":false,"given":"Kosuke","family":"Doki","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Tsukuba Hospital  Ibaraki Japan"},{"name":"Department of Pharmaceutical Sciences, Institute of Clinical Medicine University of Tsukuba  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Uda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiichiro","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Tsukuba Hospital  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Homma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Tsukuba Hospital  Ibaraki Japan"},{"name":"Department of Pharmaceutical Sciences, Institute of Clinical Medicine University of Tsukuba  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