Abstract | PURPOSE: EXPERIMENTAL DESIGN: The pharmacokinetics and metabolism of cyclophosphamide were studied during a single course of treatment in 36 children receiving a uniform chemotherapy regimen for B-cell non-Hodgkin's lymphoma and were analyzed in terms of disease recurrence and hematological toxicity. RESULTS: At a median follow-up of 43 months (range, 17-98 months), six children had developed recurrent disease, giving an overall disease-free survival of 83%. The median clearance of cyclophosphamide in patients who remain free of B-cell non-Hodgkin's lymphoma was 3.7 liter/h/m(2) (range, 2.3-5.0 liter/h/m(2)), compared with 2.2 (range, 1.5-2.5 liter/h/m(2)) in those with disease recurrence. Likelihood of recurrence was higher in patients with low clearance (<3.5 liter/h/m(2)) of cyclophosphamide (P < 0.01) and positively related to detection of the inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide in plasma (P = 0.01). There was no correlation between cyclophosphamide metabolism and hematological toxicity. CONCLUSIONS: Inadequate clearance of cyclophosphamide to active metabolites is associated with increased risk of recurrence of B-cell non-Hodgkin's lymphoma in children. Modified chemotherapy strategies should be considered in patients who exhibit low rates of clearance of the parent drug and/or extensive production of inactive metabolites.
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Authors | S Murray Yule, Lisa Price, Alex D McMahon, Andrew D J Pearson, Alan V Boddy |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 2
Pg. 455-60
(Jan 15 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 14760065
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Phosphoramide Mustards
- Cyclophosphamide
- carboxyphosphamide
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Topics |
- Adolescent
- Antineoplastic Agents, Alkylating
(pharmacokinetics)
- Child
- Child, Preschool
- Cyclophosphamide
(pharmacokinetics)
- Disease-Free Survival
- Female
- Humans
- Lymphoma, B-Cell
(drug therapy, metabolism, pathology)
- Lymphoma, Non-Hodgkin
(drug therapy, metabolism, pathology)
- Male
- Phosphoramide Mustards
(pharmacology)
- Recurrence
- Time Factors
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