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Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4068-71.

Flat-fixed dosing of irinotecan: influence on pharmacokinetic and pharmacodynamic variability.

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  • 1Department of Medical Oncology, Erasmus University MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

Abstract

PURPOSE:

In a previous analysis, it was shown that body-surface area (BSA) is not a predictor of irinotecan pharmacokinetic parameters. Here, we prospectively evaluated the effects of administering a flat-fixed irinotecan dose to cancer patients, regardless of BSA.

EXPERIMENTAL DESIGN:

Twenty-six cancer patients (12 females) received a fixed irinotecan dose of 600 mg, given as a 90-min i.v. infusion. Plasma concentrations of irinotecan and its metabolites SN-38 (7-ethyl-10-hydroxycamptothecin) and SN-38G (SN-38 glucuronide) were measured during the first cycle and analyzed using nonlinear mixed-effect modeling. Data were compared with those obtained in 47 cancer patients (19 females) who received irinotecan at a BSA-normalized dose of 350 mg/m(2).

RESULTS:

The interindividual variability in irinotecan clearance (25.9% versus 25.1%; P = 0.93), in relative extent of conversion to SN-38 (47.8% versus 42.7%; P = 0.24), and in relative extent of SN-38 glucuronidation (71.2% versus 72.4%; P = 0.95) were not significantly different between the two dose groups. Variance differences in irinotecan-mediated hematological side effects were also similar between the 600 mg and 350 mg/m(2) groups (P > 0.14).

CONCLUSIONS:

These findings suggest that flat-fixed dosing of irinotecan does not result in increased pharmacokinetic/pharmacodynamic variability and could be safely used to supplant current dosing strategies based on BSA.

PMID:
15217940
[PubMed - indexed for MEDLINE]
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