Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter?
OBJECTIVE
The purpose of this study was to determine the potential utility of alternative weight descriptors in the Cockcroft-Gault equation to more accurately predict carboplatin clearance in underweight, normal weight, overweight and obese patients.


METHODS
Clearance values obtained from individual fits using NONMEM were compared to predicted carboplatin clearances calculated using the modified Calvert formula in which creatinine clearance was calculated with the Cockcroft-Gault equation using diverse weight descriptors.


RESULTS
This study indicated that lean body mass was the best weight descriptor in underweight and normal weight patients, while adjusted ideal body weight was the best weight descriptor in overweight and obese patients. However, a flat dose based on the population carboplatin clearance performed better in all weight categories than the use of the Cockcroft-Gault equation with diverse weight descriptors.


CONCLUSIONS
These results suggest that in overweight and obese patients, with a normal renal function, a flat carboplatin dose should be administered, based on the population carboplatin clearance (8.38 l/h = 140 mL/min). Thus, in case an AUC of 5 mg min/mL is desired, the appropriate dose for carboplatin would be 5 x 140 = 700 mg.
Ekhart
Corine
C
Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Corine.Ekhart@slz.nl
Rodenhuis
Sjoerd
S
Schellens
Jan H M
JH
Beijnen
Jos H
JH
Huitema
Alwin D R
AD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D017711:Nonlinear Dynamics; D009765:Obesity / Q000150:complications; D050177:Overweight / Q000150:complications; D055815:Young Adult
D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin