{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:21:24Z","timestamp":1786123284961,"version":"build-2736575974"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":211,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Reata Pharmaceutical Company, MDACC Institutional Core Grant","award":["CA16672"],"award-info":[{"award-number":["CA16672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This multi-institutional phase I trial aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities, pharmacokinetics, and preliminary antitumor activity of berubicin (WP744 or RTA744), designed to cross the blood\u2013brain barrier, in patients with primary brain cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-five patients with recurrent or refractory primary brain cancers, including glioblastoma multiforme, received berubicin infusions over 2 h for 3 consecutive days (one course) every 21 days. Daily doses escalated from 1.2 to 9.6 mg\/m2 using an accelerated titration design. Plasma levels of berubicin were measured via high-performance liquid chromatography\u2013tandem mass spectrometry to estimate pharmacokinetic parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The daily MTD was determined to be 7.5 mg\/m2. Nonhematological toxicities were minimal; no cardiotoxicity was observed. In the intention-to-treat population (n\u2009=\u200935), 1 patient had a durable complete response, 1 had a partial response, and 9 had stable disease, corresponding to an objective response rate of 5.7% and a disease control rate of 31.4%. In the response-evaluable subset (n\u2009=\u200925), the corresponding rates were 8% and 44%, respectively; these secondary estimates should be interpreted with caution as patients who discontinued early were excluded. Pharmacokinetic analysis determined a mean half-life of 32.8 h. The area under the curve increased proportionally with dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The tolerability and efficacy of berubicin, including one durable complete response, warrant continued development of the molecule. Berubicin shows activity over a range of doses, including a durable response at 2.4 mg\/m2. The recommended phase II dose is 7.5 mg\/m2 infusions over 2 h for 3 days every 3 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>NCT00526812.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag150","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:51:33Z","timestamp":1785498693000},"source":"Crossref","is-referenced-by-count":0,"title":["Phase I trial and pharmacokinetic study of berubicin (RTA 744) in patients with recurrent or refractory high-grade gliomas"],"prefix":"10.1093","volume":"8","author":[{"given":"Charles A","family":"Conrad","sequence":"first","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center , Houston, Texas,","place":["USA"]},{"name":"US Oncology , The Woodlands , Texas, (C.A.C., M.R. G.)","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigmund H","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center , Houston, Texas,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Thapar","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplantation, The University of Texas M.D. Anderson Cancer Center , Houston, Texas,","place":["USA"]},{"name":"Reata Pharmaceutical Inc ., Dallas, Texas,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Maher","sequence":"additional","affiliation":[{"name":"Center for Neuro-Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts,","place":["USA"]},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School , Boston, Massachusetts,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy F","family":"Cloughesy","sequence":"additional","affiliation":[{"name":"Department of Neurology and Henry E. Singleton Brain Tumor Program, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, California,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Colman","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center , Houston, Texas,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center , Houston, Texas,","place":["USA"]},{"name":"National Cancer Institute , Bethesda, Maryland,","place":["USA"]},{"name":"US Oncology , The Woodlands , Texas, (C.A.C., M.R. 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