Cyclophosphamide metabolism in children with non-Hodgkin's lymphoma.

Abstract

PURPOSE:

The purpose of our study was to determine whether variation in cyclophosphamide metabolism influences the incidence of recurrence among children receiving chemotherapy for B-cell non-Hodgkin's lymphoma.

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.

• 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)

Chemical References

• Antineoplastic Agents, Alkylating
• Phosphoramide Mustards
• Cyclophosphamide
• carboxyphosphamide

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