TY - JOUR
T1 - Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese
AU - Sparreboom, A
AU - Wolff, AC
AU - Mathijssen, RHJ
AU - Chatelut, E
AU - Rowinsky, EK
AU - Verweij, Jaap
AU - Baker, SD
PY - 2007/10/20
Y1 - 2007/10/20
N2 - PURPOSE: Despite the rising prevalence of obesity, there is paucity of information describing how doses of anticancer drugs should be adjusted in clinical practice. Here, we assessed the pharmacokinetics of eight anticancer drugs in adults and evaluated the potential utility of alternative weight descriptors in dose calculation for the obese.PATIENTS AND METHODS: A total of 1,206 adult cancer patients were studied, of whom 162 (13.4%) were obese (body mass index > or = 30). Pharmacokinetic parameters were calculated using noncompartmental analysis, and compared between lean (body mass index < or = 25) and obese patients.RESULTS: The absolute clearance of cisplatin, paclitaxel, and troxacitabine was significantly increased in the obese (P < .023), but this was not observed for carboplatin, docetaxel, irinotecan, or topotecan (P < .17). For doxorubicin, the systemic clearance was statistically significantly reduced in obese women (P = .013), but not in obese men (P = .52). Evaluation of alternate weight descriptors for dose calculation in the obese, including predicted normal weight, lean body mass, (adjusted) ideal body weight, and the mean of ideal and actual body weight, indicated that, for most of the evaluated drugs, weight scalars used to calculate body-surface area should consider actual body weight regardless of size.CONCLUSION: The results suggest that a number of widely used empiric strategies for dose adjustments in obese patients, including a priori dose reduction or dose capping, should be discouraged.
AB - PURPOSE: Despite the rising prevalence of obesity, there is paucity of information describing how doses of anticancer drugs should be adjusted in clinical practice. Here, we assessed the pharmacokinetics of eight anticancer drugs in adults and evaluated the potential utility of alternative weight descriptors in dose calculation for the obese.PATIENTS AND METHODS: A total of 1,206 adult cancer patients were studied, of whom 162 (13.4%) were obese (body mass index > or = 30). Pharmacokinetic parameters were calculated using noncompartmental analysis, and compared between lean (body mass index < or = 25) and obese patients.RESULTS: The absolute clearance of cisplatin, paclitaxel, and troxacitabine was significantly increased in the obese (P < .023), but this was not observed for carboplatin, docetaxel, irinotecan, or topotecan (P < .17). For doxorubicin, the systemic clearance was statistically significantly reduced in obese women (P = .013), but not in obese men (P = .52). Evaluation of alternate weight descriptors for dose calculation in the obese, including predicted normal weight, lean body mass, (adjusted) ideal body weight, and the mean of ideal and actual body weight, indicated that, for most of the evaluated drugs, weight scalars used to calculate body-surface area should consider actual body weight regardless of size.CONCLUSION: The results suggest that a number of widely used empiric strategies for dose adjustments in obese patients, including a priori dose reduction or dose capping, should be discouraged.
U2 - 10.1200/JCO.2007.11.2938
DO - 10.1200/JCO.2007.11.2938
M3 - Article
C2 - 17947717
SN - 0732-183X
VL - 25
SP - 4707
EP - 4713
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -
