Biochemical parameters
As a part of standard hospital protocol haematology and biochemistry
assessments were done before every chemo course: aminotransferase
(ASAT), alanine-amino transferase (ALAT), gamma-glutamyltransferase
(GGT), alkaline phosphatase (ALP), alpha-1-acidglycoprotein (AAG),
albumin (ALB), total bilirubin, creatinine, haemoglobin (Hb), hematocrit
(Ht), red cell count (RBC), platelat count, total white cell count (WBC)
and diffferential white cell count.
Data and statistical analysis Data were expressed as median with their interquartile range (IQR).
Comparison between median values obtained in females and males were made
using the Mann-Whitney U test for unpaired data. The accepted
significance level was p<0.05. Linear regression analysis was
used to compare correlations of BSA, LBM and TBW with docetaxel
clearance and exposure. Correlations were therefore evaluated by
determining Spearman correlation coefficients with corresponding p
values.
Different doses were simulated, based on individual anthropometric and
body composition parameters and median docetaxel/BSA, docetaxel/LBM,
docetaxel/TBW and docetaxel dose (referred as fixed dose). An optimal
target AUC was assumed to be the recommended docetaxel dose of 75
mg/m2 divided by all individual clearance values
corrected for BSA.
The difference between the optimal target AUC and simulated AUC results
was evaluated by calculating accuracy using mean absolute percentage
error (MAPE):
\begin{equation}
\mathrm{MAPE=}\frac{\mathrm{1}}{\mathrm{n}}\mathrm{\ }\sum{\mathrm{|}\frac{\mathrm{\text{AUCsim}}\mathrm{\ }\mathrm{-}\mathrm{\ }\mathrm{\text{AUCtarget}}}{\mathrm{\text{AUCtarget}}}}\mathrm{|\ x\ 100}\mathrm{,}\nonumber \\
\end{equation}where AUCsim denotes the simulated AUC results and AUCtarget denotes the
optimal target AUC.
Bias was calculated using the mean error (ME):
\begin{equation}
\mathrm{ME=\ }\frac{\mathrm{1}}{\mathrm{n}}\mathrm{\ }\sum{\left(\mathrm{\text{AUCsim}}\mathrm{\ }\mathrm{-}\mathrm{\ }\mathrm{\text{AUCtarget}}\right)\mathrm{,}}\nonumber \\
\end{equation}where AUCsim denotes the simulated AUC results and AUCtarget denotes the
optimal target AUC.
Toxicity Toxicity due to chemotherapy was scored by the physicians during all
treatment cycles according to the Common Terminology Criteria for
Adverse Events (CTCAE) v 4.0 criteria.30 Only grade 3
and 4 toxicities were considered in the analysis. Premature therapy
termination (patient does not complete the standard 6 or 10 cycles),
dose delay (patient needs more than 3 weeks to recover from
chemotherapy) and dose reduction because of toxicity, were recorded.
Overall toxicity was defined when; any toxicity ≥ grade 3, and/or dose
delay, dose reduction and premature treatment termination occurred due
to toxicity.