Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Sparreboom
Alex
A
Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. alex.sparreboom@stjude.org
Wolff
Antonio C
AC
Mathijssen
Ron H J
RH
Chatelut
Etienne
E
Rowinsky
Eric K
EK
Verweij
Jaap
J
Baker
Sharyn D
SD
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015992:Body Mass Index; D049628:Body Size; D001830:Body Surface Area; D001835:Body Weight; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004148:Dioxolanes / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008657:Metabolic Clearance Rate; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage
D004148:Dioxolanes; D043823:Taxoids; D000077143:Docetaxel; C074908:troxacitabine; D000077146:Irinotecan; D019772:Topotecan; D004317:Doxorubicin; D003596:Cytosine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin