{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:15:01Z","timestamp":1772770501109,"version":"3.50.1"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary response rate for ixabepilone, a microtubule-stabilizing agent, administered intravenously daily for 5 days in children and adolescents. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients \u2265 2 and \u2264 18 years with relapsed or refractory solid tumors were enrolled onto sequential cohorts to the following five dose levels: 3.0 (n = 3), 4.5 (n = 4), 6.0 (n = 3), 8.0 (n = 6), and 10 (n = 3) mg\/m<jats:sup>2<\/jats:sup>\/d. Eligibility criteria, dose levels, definitions of DLT and MTD, and pharmacokinetic sampling times were designed to be as similar as possible to the adult phase I trial of ixabepilone on the same schedule. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Nineteen children (median age, 10 years; range, 2 to 18 years) were enrolled, and 18 (12 with sarcomas) were assessable for toxicity. DLTs (grade 4 neutropenia for &gt; 5 days and grade 3 fatigue) were observed in two of three patients receiving 10 mg\/m<jats:sup>2<\/jats:sup>\/d. The MTD of ixabepilone administered daily for 5 days every 21 days was 8 mg\/m<jats:sup>2<\/jats:sup>\/d. Myelosuppression, GI, and hepatic toxicities were common non-DLTs. Peripheral neuropathy was uncommon. Ixabepilone clearance was 475 \u00b1 247 mL\/min\/m<jats:sup>2<\/jats:sup>, volume of distribution at steady-state was 12.2 \u00b1 5.4 L\/kg, and half-life was 14 hours. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The recommended dose of ixabepilone for phase II trials in solid tumors is 8 mg\/m<jats:sup>2<\/jats:sup>\/d daily for 5 days every 21 days. This dose is 33% higher than the MTD in adults receiving the same dosing schedule. Pharmacokinetic parameters in children and adolescents were highly variable but similar to adults. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2008.17.6644","type":"journal-article","created":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T02:43:27Z","timestamp":1229395407000},"page":"550-556","source":"Crossref","is-referenced-by-count":23,"title":["Phase I Trial and Pharmacokinetic Study of Ixabepilone Administered Daily for 5 Days in Children and Adolescents With Refractory Solid Tumors"],"prefix":"10.1200","volume":"27","author":[{"given":"Brigitte C.","family":"Widemann","sequence":"first","affiliation":[{"name":"From the Pediatric and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Goodspeed","sequence":"additional","affiliation":[{"name":"From the Pediatric and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 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