Effect of body mass index on pharmacokinetics of paclitaxel in patients with early breast cancer

Cancer Medicine

Navin Goyal¹  Anand Patil²  Manjunath Nookala²  Murari Gurjar²  Ashwin Karanam²  Vikram Gota²  Bharati Shriyan²  Yogesh Kembhavi³  Ashish Singh³  Sudeep Gupta⁴  Avinash Bonda⁴ 

[1] Clinical PharmacologyGlaxoSmithKline Pennsylvania PA USA;Department of Clinical Pharmacology Advanced Centre for Treatment, Research and Education in Cancer Tata Memorial Centre Navi Mumbai India;Department of Medical Oncology Tata Memorial Centre Mumbai India;Homi Bhabha National Institute Mumbai India;

关键词: body surface area;    breast cancer;    paclitaxel;    pharmacokinetics;   

DOI  :  10.1002/cam4.3865

来源: DOAJ

【 摘 要 】

ABSTRACT Background Paclitaxel is dosed according to body surface area (BSA) but there is scant information on actual drug exposure in overweight and obese patients. Methods Early breast cancer patients receiving paclitaxel at 175 mg/m2 every 3 weeks, in two BMI groups (normal, 18–24.9 kg/m2 and overweight/obese, ≥25 kg/m2, respectively), matched for age, serum albumin and bilirubin levels using minimization technique, were included. Sparse pharmacokinetic (PK) sampling was performed at 7 time points from 0 h until 24 h of starting paclitaxel in cycle 1. Paclitaxel concentration was measured using a validated LCMS/MS method. Covariate effect on paclitaxel PK was evaluated by population PK analysis using NONMEM software. Results Eighteen female patients each were enrolled in normal and overweight groups with mean BMI of 21.62 ± 2.06 and 28.16 ± 2.31 kg/m2, mean BSA of 1.44 ± 0.11 and 1.69 ± 0.14 m2 and mean paclitaxel dose of 250 ± 18 and 293 ± 21 mg, respectively. Model predicted AUC and dose normalized AUC (mean ±SD) in the normal BMI versus overweight obese groups were 23 ± 11.0 µmol*h/L versus 25.7 ± 13.7 µmol*h/L (two‐sample t‐test p > 0.05) and 0.08 ± 0.04 (µmol*h/L)/ µmol versus 0.08 ± 0.04 (µmol*h/L)/ µmol (2‐sample t‐test p > 0.05), respectively. No significant correlation was observed between BMI and standardized dose normalized AUC (Pearson's correlation coefficient, −0.009; p > 0.05). Conclusion When dosed according to BSA calculated using actual body weight there is no significant difference in paclitaxel exposure between normal and overweight women. Using alternative descriptors of weight to calculate BSA could lead to under‐dosing of this drug. Trial registration This study is registered in the Clinical Trials Registry of India CTRI/2015/09/006193.

【 授权许可】

Unknown