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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2010

01-04-2010 | Original Article

Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression

Authors: Emma K. Hansson, Johan E. Wallin, Henrik Lindman, Marie Sandström, Mats O. Karlsson, Lena E. Friberg

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2010

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Abstract

Purpose

A previously developed semi-physiological model of chemotherapy-induced myelosuppression has shown consistent system-related parameter and inter-individual variability (IIV) estimates across drugs. A requirement for dose individualization to be useful is relatively low variability between treatment courses (inter-occasion variability [IOV]) in relation to IIV. The objective of this study was to evaluate and compare magnitudes of IOV and IIV in myelosuppression model parameters across six different anti-cancer drug treatments.

Methods

Neutrophil counts from several treatment courses following therapy with docetaxel, paclitaxel, epirubicin-docetaxel, 5-fluorouracil–epirubicin–cyclophosphamide, topotecan, and etoposide were included in the analysis. The myelosuppression model was fitted to the data using NONMEM VI. IOV in the model parameters baseline neutrophil counts (ANC0), mean transit time through the non-mitotic maturation chain (mean transit time [MTT]), and the parameter describing the concentration–effect relationship (slope), were evaluated for statistical significance (P < 0.001).

Results

Inter-occasion variability in MTT was significant for all the investigated datasets, except for topotecan, and was of similar magnitude (8–16 CV%). IOV in slope was significant for docetaxel, topotecan, and etoposide (19–39 CV%). For all six investigated datasets, the IOV in myelosuppression parameters was lower than the IIV. There was no indication of systematic shifts in the system- or drug sensitivity-related parameters over time across datasets.

Conclusion

This study indicates that the semi-physiological model of chemotherapy-induced myelosuppression has potential to be used for prediction of the time-course of myelosuppression in future courses and is, thereby, a valuable step towards individually tailored anticancer drug therapy.
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Metadata
Title
Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression
Authors
Emma K. Hansson
Johan E. Wallin
Henrik Lindman
Marie Sandström
Mats O. Karlsson
Lena E. Friberg
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-009-1089-3

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