Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia

Jane S. Hankins, Lynn W. Wynn, Carlo Brugnara, Cheryl A. Hillery, Chin-Shang Li, Winfred C. Wang

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

In sickle cell anaemia, red cell dehydration increases intracellular HbS concentration and promotes sickling. Higher erythrocyte magnesium reduces water loss through negative regulation of membrane transporters. Hydroxycarbamide (also known as hydroxyurea) reduces sickling partly by increasing intracellular HbF. Combining drugs with distinct mechanisms could offer additive effects. A phase I trial combining oral magnesium pidolate and hydroxycarbamide was performed to estimate the maximum tolerated dose (MTD) and toxicity of magnesium. Cohorts of three children with HbSS, who were on a stable dose of hydroxycarbamide (median 28.5 mg/kg/d), received magnesium pidolate for 6 months beginning at 83 mg/kg/d. The dose was escalated by 50% for subsequent cohorts. Laboratory evaluations were performed at 0, 3, 6 and 9 months. Sixteen children (aged 4-12 years) participated. All four dose-limiting toxicities (grade III diarrhoea and abdominal pain) occurred within the first month of starting magnesium. Additionally, diarrhoea grades I (n = 1) and II (n = 3), and abdominal pain grade II (n = 3) occurred. Hydroxycarbamide dose reduction or interruption was not required. The MTD for magnesium pidolate used in combination with hydroxycarbamide was 125 mg/kg/d. KCl co-transporter activity declined after 3 months of magnesium pidolate (P = 0.02). A phase II study is needed to investigate the efficacy of this drug combination.

Original languageEnglish (US)
Pages (from-to)80-85
Number of pages6
JournalBritish Journal of Haematology
Volume140
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Hydroxycarbamide
  • Magnesium pidolate
  • Red cell dehydration
  • Sickle cell anaemia

ASJC Scopus subject areas

  • Hematology

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