{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:45:09Z","timestamp":1790775909714,"version":"4.1.0"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2006,8,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the histone deacetylase inhibitor, depsipeptide, in children with refractory or recurrent solid tumors. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Depsipeptide was administered as a 4-hour infusion weekly for 3 consecutive weeks every 28 days at dose levels of 10 mg\/m<jats:sup>2<\/jats:sup>, 13 mg\/m<jats:sup>2<\/jats:sup>, 17 mg\/m<jats:sup>2<\/jats:sup>, and 22 mg\/m<jats:sup>2<\/jats:sup>. Pharmacokinetics and histone acetylation studies were performed in the first course. The levels of H3 histone and acetyl-H3 histone were evaluated in peripheral blood mononuclear cells (PBMC) using immunofluorescence techniques. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> There were 24 patients, and 18 who were assessable were enrolled. DLTs included reversible, asymptomatic T-wave inversions, without any associated changes in troponin levels or evidence of ventricular dysfunction, in the inferior leads in two patients at 22 mg\/m<jats:sup>2<\/jats:sup> and in the lateral leads in one patient at 13 mg\/m<jats:sup>2<\/jats:sup> (n = 1), and transient asymptomatic sick sinus syndrome and hypocalcemia in one patient at 17 mg\/m<jats:sup>2<\/jats:sup>. At the MTD (17 mg\/m<jats:sup>2<\/jats:sup>), the median depsipeptide clearance was 6.8 L\/h\/m<jats:sup>2<\/jats:sup> with an area under the plasma depsipeptide concentration-time curve from 0 to infinity of 2,414 ng\/mL\/h, similar to adults. Accumulation of acetylated H3 histones was seen in all patients in a dose independent manner, with maximal accumulation at a median of 4 hours, (range, 0 hours to 20 hours) after the end of the infusion. No objective tumor responses were observed. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Depsipeptide is well tolerated in children with recurrent or refractory solid tumors when administered weekly for 3 consecutive weeks every 28 days and inhibits histone deacetylase activity in PBMC in a dose-independent manner. The recommended phase II dose in children with solid tumors is 17 mg\/m<jats:sup>2<\/jats:sup>. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2006.06.4964","type":"journal-article","created":{"date-parts":[[2006,7,28]],"date-time":"2006-07-28T23:30:31Z","timestamp":1154129431000},"page":"3678-3685","source":"Crossref","is-referenced-by-count":74,"title":["Phase I Study of Depsipeptide in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Report"],"prefix":"10.1200","volume":"24","author":[{"given":"Maryam","family":"Fouladi","sequence":"first","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology and Pharmaceutical Sciences, St Jude Children's Research Hospital; Keck School of Medicine, University of Southern California, Los Angeles; Children's Oncology Group Operations Center, Arcadia, CA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; Children's Hospital of Philadelphia, Philadelphia, PA; Texas Children's Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne L.","family":"Furman","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology and Pharmaceutical Sciences, St Jude Children's Research Hospital; Keck School of Medicine, University of Southern California, Los Angeles; Children's Oncology Group Operations Center, Arcadia, CA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN; Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; Children's Hospital of Philadelphia, Philadelphia, PA; Texas Children's Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Chin","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology and Pharmaceutical Sciences, St Jude Children's Research Hospital; 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