{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:12:42Z","timestamp":1791198762790,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,12,7]],"date-time":"2016-12-07T00:00:00Z","timestamp":1481068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007313","name":"University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["CA016672"],"award-info":[{"award-number":["CA016672"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Phosphatidylinositol\u20103\u2010kinase (PI3K) signaling plays a crucial role in oncogene\u2010mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan\u2010class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed\/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM\u2010120 80 mg\/day and two 100 mg\/day. The MTD was 80 mg\/day. Of the 14 patients treated, the best response was stable disease in one patient that lasted 82 days. The median survival for all patients was 75 days (range 10\u2013568). Three patients with a 3q26 chromosome abnormality had a significantly improved median survival of 360 days (range 278\u2013568) as compared to a median survival of 57 days (range, 10\u2013125) among the 11 other patients. The most frequent drug\u2010related toxicities included confusion, mucositis, dysphagia, and fatigue. Western blot profiling revealed a decrease in p\u2010pS6K\/total pS6K in 5\/7 (71%) available patient samples with a mean quantitative inhibition of 65% (range, 32\u2013100%) and a decrease in p\u2010FOXO3\/total FOXO3 in 4\/6 (67%) samples with a mean quantitative inhibition of 93% (range, 89\u2013100%). BKM120 administered at 80 mg\/day showed modest efficacy and was tolerable in advanced acute leukemias. Am. J. Hematol. 92:7\u201311, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24568","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T22:51:06Z","timestamp":1475016666000},"page":"7-11","source":"Crossref","is-referenced-by-count":49,"title":["Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias"],"prefix":"10.1002","volume":"92","author":[{"given":"Brittany Knick","family":"Ragon","sequence":"first","affiliation":[{"name":"Hematology\/Oncology Fellowship, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center Houston 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