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Blood, 15 January 2008, Vol. 111, No. 2, pp. 566-573. Prepublished online as a Blood First Edition Paper on October 24, 2007; DOI 10.1182/blood-2007-08-107839. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-08-107839v1 111/2/566    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fox, E. Articles by Adamson, P. C. Search for Related Content PubMed PubMed Citation Articles by Fox, E. Articles by Adamson, P. C. Related Collections Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma Elizabeth Fox1, Bassem I. Razzouk2,3, Brigitte C. Widemann1, Shaun Xiao1, Michelle O'Brien1, Wendy Goodspeed1, Gregory H. Reaman4, Susan M. Blaney5, Anthony J. Murgo6, Frank M. Balis1, and Peter C. Adamson7 1 Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD; 2 St Jude Children's Research Hospital, Memphis, TN; 3 St Vincent Children's Hospital, Indianapolis, IN; 4 Children's Oncology Group, Arcadia, CA; 5 Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX; 6 Cancer Therapy and Evaluation Program, NCI, Bethesda, MD; and 7 Children's Hospital of Philadelphia, PA Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n = 13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n = 2) or 0.2 mg/kg per day (n = 4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non–dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (Cmax) was 0.28 µM (0.11-0.37 µM) and at 0.2 mg/kg per day, Cmax was 0.40 and 0.46 µM; area under the concentration times time curve (AUC0-24) was 2.50 µM-hr (1.28-3.85 µM-hr) and 4.37 µM-hr and 4.69 µM-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 [ClinicalTrials.gov] at www.ClinicalTrials.gov. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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