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Lean body mass and total body weight versus body surface area as determinant of docetaxel pharmacokinetics and toxicity
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  • Rien Hoge,
  • Suzan Detert Oude Weme,
  • Walter Vervenne,
  • Inge van Berlo - van de Laar,
  • Carla van Herpen,
  • Laurens Roorda,
  • Ron Mathot,
  • Maartje Jacobs,
  • Nielka Van Erp,
  • Frank Jansman
Rien Hoge
Wilhelmina Hospital Assen

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Suzan Detert Oude Weme
Deventer Hospital
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Walter Vervenne
Deventer Hospital
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Inge van Berlo - van de Laar
Deventer Ziekenhuis
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Carla van Herpen
Radboud university medical center Nijmegen
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Laurens Roorda
Wilhelmina Hospital Assen
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Ron Mathot
Amsterdam UMC - Locatie AMC
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Maartje Jacobs
University of Groningen
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Nielka Van Erp
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Frank Jansman
University of Groningen
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Abstract

Aim: In our study we examined whether anthropometric and body composition parameters, i.e. body surface area (BSA), lean body mass (LBM) and total body weight (TBW), are correlated with docetaxel clearance and exposure. In addition, LBM, TBW and a fixed dose were compared to BSA as dosing parameters for dose individualisation of docetaxel. Methods: Thirty-six patients affected by breast or castration-resistant prostate carcinoma receiving docetaxel chemotherapy entered the study. LBM was measured by a Dual Energy Xray Absorptiometry (DEXA) scanner before treatment. Blood samples were collected up to 180 minutes after dosing to analyse docetaxel concentrations and to determine individual pharmacokinetic (PK) parameters. Results: No significant correlations were found between the docetaxel pharmacokinetic parameters clearance and volume of distribution and the anthropometric and body composition variables BSA, LBM and TBW. AUC was significantly but poorly correlated with BSA (r=0.452 [p=0.016]) and with TBW (r=0.476 (p=0.011]). The Mean Absolute Percentage Error and Mean Error of simulated dosing based on LBM and fixed dosing ME were not significant different compared to BSA. For TBW, only the MAPE of dosing was significant higher compared to BSA (24.1 vs. 17.1, P=0.001). Conclusion: There is no correlations between docetaxel pharmacokinetics and the anthropometric and body composition variables BSA, LBM and TBW. Dose individualisation of docetaxel based on LBM or TBW or fixed dosing cannot be recommended over BSA based dosing.
24 Aug 2022Published in Therapeutic Drug Monitoring volume Publish Ahead of Print. 10.1097/FTD.0000000000001029