{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:14:42Z","timestamp":1792239282994,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1CA081457"],"award-info":[{"award-number":["UM1CA081457"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood cancer with median survival of less than 1 year. Panobinostat is an oral multihistone deacetylase inhibitor with preclinical activity in DIPG models. Study objectives were to determine safety, tolerability, maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics of panobinostat in children with DIPG.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>In stratum 1, panobinostat was administered 3 days per week for 3 weeks on, 1 week off to children with progressive DIPG, with dose escalation following a two-stage continual reassessment method. After this MTD was determined, the study was amended to evaluate the MTD in children with nonprogressive DIPG\/Diffuse midline glioma (DMG) (stratum 2) on an alternate schedule, 3 days a week every other week in an effort to escalate the dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For stratum 1, 19 subjects enrolled with 17\/19 evaluable for dose-finding. The MTD was 10 mg\/m2\/dose. Dose-limiting toxicities included thrombocytopenia and neutropenia. Posterior reversible encephalopathy syndrome was reported in 1 patient. For stratum 2, 34 eligible subjects enrolled with 29\/34 evaluable for dose finding. The MTD on this schedule was 22 mg\/m2\/dose. DLTs included thrombocytopenia, neutropenia, neutropenia with grade 4 thrombocytopenia, prolonged intolerable nausea, and increased ALT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The MTD of panobinostat is 10 mg\/m2\/dose administered 3 times per week for 3 weeks on\/1 week off in children with progressive DIPG\/DMG and 22 mg\/m2\/dose administered 3 times per week for 1 week on\/1 week off when administered in a similar population preprogression. The most common toxicity for both schedules was myelosuppression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noad141","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T13:47:23Z","timestamp":1690897643000},"page":"2262-2272","source":"Crossref","is-referenced-by-count":68,"title":["Phase I trial of panobinostat in children with diffuse intrinsic pontine glioma: A report from the Pediatric Brain Tumor Consortium (PBTC-047)"],"prefix":"10.1093","volume":"25","author":[{"given":"Michelle","family":"Monje","sequence":"first","affiliation":[{"name":"Department of Neurology, Stanford University and Lucile Packard Children\u2019s Hospital , Palo Alto, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabitha","family":"Cooney","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Dana Farber Cancer Institute\/Boston Children\u2019s Hospital , Boston, MA , 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CANADA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3703-8742","authenticated-orcid":false,"given":"Patricia","family":"Baxter","sequence":"additional","affiliation":[{"name":"Pediatric Oncology, Texas Children\u2019s Cancer Center , Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center , New York , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Lenzen","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology, Lurie Children\u2019s Hospital , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J","family":"Robison","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Kilburn","sequence":"additional","affiliation":[{"name":"Department of Oncology, Children\u2019s National Hospital , Washington, DC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vinitsky","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St. Jude Children\u2019s Research Hospital , Memphis, TN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-2606","authenticated-orcid":false,"given":"William D","family":"Figg","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Clinical Pharmacology Program, National Cancer Institute , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Jabado","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Center , Montreal, Quebec CANADA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-035X","authenticated-orcid":false,"given":"Maryam","family":"Fouladi","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Oncology, Nationwide Children\u2019s Hospital , Columbus, OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-5259","authenticated-orcid":false,"given":"Jason","family":"Fangusaro","sequence":"additional","affiliation":[{"name":"Department: Pediatric Hematology\/Oncology and Stem Cell Transplantation , Atlanta, GA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Onar-Thomas","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St. Jude Children\u2019s Research Hospital , Memphis, TN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira 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