High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy

M. E. De Jonge, A. D.R. Huitema, J. H. Beijnen, S. Rodenhuis

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66 Citations (Scopus)

Abstract

We investigated whether the occurrence of veno-occlusive disease of the liver (VOD) may be associated with individual variations in the pharmacokinetics of high-dose cyclophosphamide. Patients received single or multiple courses of cyclophosphamide (1000 or 1500 mg m-2 day-1), thiotepa (80 or 120 mg m-2 day-1) and carboplatin (265-400 mg m -2 day-1) (CTC) for 4 consecutive days. The area under the plasma concentration-time curves (AUCs) were calculated for cyclophosphamide and its activated metabolites 4-hydroxycyclophosphamide and phosphoramide mustard based on multiple blood samples. Possible relationships between the AUCs and the occurrence of VOD were studied. A total of 59 patients (115 courses) were included. Four patients experienced VOD after a second CTC course. The first-course AUC of 4-hydroxycyclophosphamide (P = 0.003) but not of phosphoramide mustard (P = 0.101) appeared to be predictive of the occurrence of VOD after multiple courses. High exposures to bioactivated cyclophosphamide may lead to increased organ toxicity.

Original languageEnglish
Pages (from-to)1226-1230
Number of pages5
JournalBritish Journal of Cancer
Volume94
Issue number9
DOIs
Publication statusPublished - 8 May 2006
Externally publishedYes

Keywords

  • Bioactivation
  • Correlation
  • Cyclophosphamide
  • Exposure
  • Veno-occlusive disease

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