{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:08:29Z","timestamp":1783573709435,"version":"3.55.0"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd \u00d7 5 \u00d7 2) in pediatric patients with refractory solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Cohorts of two to six patients received oral topotecan at 0.8, 1.1, 1.4, 1.8, and 2.3 mg\/m<jats:sup>2<\/jats:sup>\/d every 28 days for a maximum of six courses. Twenty patients (median age, 10.6 years) received a total of 51 courses. Eight patients received topotecan capsules during course 2 only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dose-limiting toxicity occurred at 2.3 mg\/m<jats:sup>2<\/jats:sup>\/d and consisted of prolonged grade 4 neutropenia (n = 2), grade 3 stomatitis as a result of radiation recall (n = 1), grade 3 hemorrhage (epistaxis) in the presence of grade 4 thrombocytopenia (n = 1), and grade 3 diarrhea in the presence of Clostridium difficile infection (n = 1). Dose-limiting, prolonged grade 4 neutropenia and thrombocytopenia occurred in one patient at 1.4 mg\/m<jats:sup>2<\/jats:sup>\/d. Infrequent toxicities were mild nausea, vomiting, elevated liver ALT or AST, and rash. The maximum-tolerated dosage was 1.8 mg\/m<jats:sup>2<\/jats:sup>\/d; the mean (\u00b1 standard deviation) area under the plasma concentration-time curve for topotecan lactone at this dosage was 20.9 \u00b1 8.4 ng\/mL \u00b7 h. The population mean (\u00b1 standard error) oral bioavailability of the injectable formulation was 0.27 \u00b1 0.03; that of capsules was 0.36 \u00b1 0.06 (P = .16). Disease stabilized in nine of 19 assessable patients for 1.5 to 6 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Oral topotecan (1.8 mg\/m<jats:sup>2<\/jats:sup>\/d) on a qd \u00d7 5 \u00d7 2 schedule is well tolerated and warrants additional testing in pediatric patients.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2004.07.110","type":"journal-article","created":{"date-parts":[[2004,2,27]],"date-time":"2004-02-27T23:32:46Z","timestamp":1077924766000},"page":"829-837","source":"Crossref","is-referenced-by-count":27,"title":["Phase I and Pharmacokinetic Study of Topotecan Administered Orally Once Daily for 5 Days for 2 Consecutive Weeks to Pediatric Patients With Refractory Solid Tumors"],"prefix":"10.1200","volume":"22","author":[{"given":"Najat C.","family":"Daw","sequence":"first","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology, and Pharmaceutical Sciences, St Jude Children's Research Hospital; and the University of Tennessee Health Science Center, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M.","family":"Santana","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology, and Pharmaceutical Sciences, St Jude Children's Research Hospital; and the University of Tennessee Health Science Center, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C.","family":"Iacono","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology, and Pharmaceutical Sciences, St Jude Children's Research Hospital; and the University of Tennessee Health Science Center, Memphis, TN."}],"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; and the University of Tennessee Health Science Center, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana R.","family":"Hawkins","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology, and Pharmaceutical Sciences, St Jude Children's Research Hospital; and the University of Tennessee Health Science Center, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Houghton","sequence":"additional","affiliation":[{"name":"From the Departments of Hematology-Oncology, Molecular Pharmacology, and Pharmaceutical Sciences, St Jude Children's Research Hospital; and the University of Tennessee Health Science Center, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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