Pharmacokinetic (PK)-based dosage individualization of imatinib: evaluation of efficiency and clinical usefulness


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Inproceedings: an article in a conference proceedings.
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Poster: Summary – with images – on one page of the results of a researche project. The summaries of the poster must be entered in "Abstract" and not "Poster".
Pharmacokinetic (PK)-based dosage individualization of imatinib: evaluation of efficiency and clinical usefulness
Title of the conference
3rd Symposium of the Swiss Clinical Trial Organisation (SCTO), Personalised Medicine in Clinical Research
Gotta V., Widmer N., Decosterd L.A., Montemurro M., Leyvraz S., Chalandon Y., Heim D., Gregor M., Benz R., Leoncini-Franscini L., Baerlocher G.M., Duchosal M.A., Csajka C. (co-last), Buclin T. (co-last)
Zürich, Switzerland, June 14, 2012
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Issued date
Background: Retrospective analyses suggest that personalized PK-based dosage might be useful for imatinib, as treatment response correlates with trough concentrations (Cmin) in cancer patients. Our objectives were to improve the interpretation of randomly measured concentrations and to confirm its efficiency before evaluating the clinical usefulness of systematic PK-based dosage in chronic myeloid leukemia patients.
Methods and Results: A Bayesian method was validated for the prediction of individual Cmin on the basis of a single random observation, and was applied in a prospective multicenter randomized controlled clinical trial. 28 out of 56 patients were enrolled in the systematic dosage individualization arm and had 44 follow-up visits (their clinical follow-up is ongoing). PK-dose-adjustments were proposed in 39% having predicted Cmin significantly away from the target (1000 ng/ml). Recommendations were taken up by physicians in 57%, patients were considered non-compliant in 27%. Median Cmin at study inclusion was 754 ng/ml and differed significantly from the target (p=0.02, Wilcoxon test). On follow-up, Cmin was 984 ng/ml (p=0.82) in the compliant group. CV decreased from 46% to 27% (p=0.02, F-test).
Conclusion: PK-based (Bayesian) dosage adjustment is able to bring individual drug exposure closer to a given therapeutic target. Its influence on therapeutic response remains to be evaluated.
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23/09/2013 22:51
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08/10/2021 6:40
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