Lean body mass and total body weight versus body surface area as
determinant of docetaxel pharmacokinetics and toxicity
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.