It is common practice to dose paclitaxel according to body surface area (BSA) in women with early breast cancer (EBC). However, there is scant information on actual drug exposure in overweight/obese women and whether actual or modified weight should be used in calculating BSA. The present study evaluates effect of Body Mass Index (BMI) on pharmacokinetic (PK) profile of paclitaxel.
EBC patients in two BMI groups (normal, 18-24.9 kg/m2 and overweight/obese, ≥25 kg/m2, respectively) were enrolled. All patients received single agent paclitaxel at 175 mg/m2 q3weeks. The two groups were matched for age, albumin and bilirubin levels using a minimization technique. Sparse PK sampling was performed at 7 time points from time 0 until 24 hours of starting paclitaxel infusion in cycle 1. Paclitaxel concentration was measured using a validated LCMS/MS method. PK data was modeled using WinNonlin software and PK parameters were compared using Student's t test. Covariate effect on paclitaxel PK was evaluated by population PK analysis using NONMEM software.
Thirty-six patients (18 in each group) were enrolled with mean BMI of 21.5 ± 2.0 and 28.2 ± 2.3 kg/m2, mean BSA of 1.43 ± 0.11 and 1.69 ± 0.14 and mean paclitaxel dose of 250 ± 18 and 293 ± 20 mg, in normal and overweight/obese groups, respectively. The two groups were comparable with respect to serum albumin, bilirubin, hemoglobin and performance status. PK data was well described by a two-compartment nonlinear clearance model. Normal and overweight/obese groups had comparable AUC0-∞ (26 ± 14 vs. 24 ± 13 µg/ml*hr, p = 0.657), Cmax (7.6 ± 4 vs. 6.6 ± 3 µg/ml, p = 0.363), volume of distribution (69 ± 47 vs. 68 ± 34 L/m2, p = 0.938) and clearance (8.9 ± 4.8 vs. 9.7 ± 5.4 L/hr/m2, p = 0.637), respectively. Population PK analysis showed a significant positive correlation between BMI and paclitaxel clearance while no other covariate was significant. There was no significant difference in toxicity between the two groups.
There is no significant difference in paclitaxel exposure between normal and overweight/obese women with EBC when dosed according to BSA that is calculated using actual body weight. The latter should be used when calculating paclitaxel dose in overweight/obese patients.
Clinical trial identification
Clinical trial registry of India Identifier: CTRI/2015/09/006193
Legal entity responsible for the study
Tata Memorial Centre, Mumbai
The study was funded by Tata Memorial Centre, Mumbai, through the intramural funds
All authors have declared no conflicts of interest.