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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 20, 2007 Accepted September 28, 2007 Phase I trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia including acute promyelocytic leukemia or lymphoma A collaborative study of The Pediatric Oncology Branch, National Cancer Institute and the Children's Oncology Group Elizabeth Fox*, Bassem I Razzouk, Brigitte C Widemann, Shaun Xiao, Michelle O'Brien, Wendy Goodspeed, Gregory H Reaman, Susan M Blaney, Anthony J Murgo, Frank M Balis, and Peter C Adamson Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States St Jude Children's Research Hospital, Memphis, TN, United States St. Vincent Children's Hospital, Indianapolis, IN, United States Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, United States Cancer Therapy and Evaluation Program, National Cancer Institute, Bethesda, MD, United States Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States * Corresponding author; email: foxb{at}mail.nih.gov. Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase I trial of ATO in children (median age 13 yrs, range, 2-19) with refractory leukemia. ATO was administered IV over 2 hrs, 5 days/week for 20 doses/cycle. Patients with APL (n=13) received 0.15 mg/kg/day, and patients with other types of leukemia received 0.15 mg/kg/day (n=2) or 0.2 mg/kg/day (n=4). 19 of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg/day, 2/15 patients experienced dose-limiting QTc prolongation, pneumonitis or neuropathic pain. At 0.2 mg/kg/day, 2/4 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/day, the median (range) plasma arsenic Cmax was 0.28 (0.11-0.37) µM and at 0.2 mg/kg/d, Cmax was 0.40 and 0.46 µM; AUC0-24h was 2.50 (1.28-3.85) and 4.37 and 4.69 µM·hr, respectively. Morphologic 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/day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials.gov. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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