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Siteman Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014571","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007338","name":"Foundation for Barnes-Jewish Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007338","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Barnard Research Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Metab"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC\u2019s excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09\/09\/2020) to test the safety and tolerability of dapagliflozin (5\u00a0mg p.o.\/day\u2009\u00d7\u20092\u00a0weeks escalated to 10\u00a0mg p.o.\/day\u2009\u00d7\u20096\u00a0weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and\/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) response, CT-based volumetric body composition measurements, and plasma chemistries for measuring metabolism and tumor burden were also analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of 23 patients who were screened, 15 enrolled. One expired (due to complications from underlying disease), 2 dropped out (did not tolerate GnP chemotherapy) during the first 4\u00a0weeks, and 12 completed. There were no unexpected or serious adverse events with dapagliflozin. One patient was told to discontinue dapagliflozin after 6\u00a0weeks due to elevated ketones, although there were no clinical signs of ketoacidosis. Dapagliflozin compliance was 99.4%. Plasma glucagon increased significantly. Although abdominal muscle and fat volumes decreased; increased muscle-to-fat ratio correlated with better therapeutic response. After 8\u00a0weeks of treatment in the study, partial response (PR) to therapy was seen in 2 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. After dapagliflozin discontinuation (and chemotherapy continuation), an additional 7 patients developed the progressive disease in the subsequent scans measured by increased lesion size as well as the development of new lesions. Quantitative imaging assessment was supported by plasma CA19-9 tumor marker measurements.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Dapagliflozin is well-tolerated and was associated with high compliance in patients with advanced, inoperable PDAC. Overall favorable changes in tumor response and plasma biomarkers suggest it may have efficacy against PDAC, warranting further investigation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40170-023-00306-2","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T10:02:19Z","timestamp":1684404139000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study"],"prefix":"10.1186","volume":"11","author":[{"given":"Lauren K.","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian-Huat","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Volkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Abdiannia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zack","family":"Nigogosyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn J.","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet B.","family":"McGill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis M.","family":"McKee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maamoun","family":"Salam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong M.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karteek","family":"Popuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Tze Yang","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirza Faisal","family":"Beg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda R.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Ippolito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"issue":"1","key":"306_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. 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