Samenvatting
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.
Originele taal-2 | Engels |
---|---|
Pagina's (van-tot) | 1226-1230 |
Aantal pagina's | 5 |
Tijdschrift | British Journal of Cancer |
Volume | 94 |
Nummer van het tijdschrift | 9 |
DOI's | |
Status | Gepubliceerd - 8 mei 2006 |
Extern gepubliceerd | Ja |