Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter?

Abstract

Purpose 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. Conclusion 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 9 140 = 700 mg.

Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model of obesity-associated diabetes mellitus

“…This paucity of reliable data, at least in part, ascribed to the fact that drug development and clinical trials in oncology are generally conducted irrespective of patients' body weight, and obesity is a covariate not usually stratified in data analysis. Still, it is generally acknowledged that there are considerable alterations in the pharmacokinetics of some cytotoxic drugs in obesity, which might even lead to increased toxicity but the available data are somewhat contradictory [4][5][6]. Thompson et al [7] found no differences in pharmacokinetics of daunorubicin between obese and non-obese patients while obesity worsen outcome of patients with breast cancer on doxorubicin (chemical structure is very close to daunorubicin) + cyclophosphamide therapy [8].…”

Nab-Paclitaxel and Carboplatin (Nab-PC) Regimen for Advanced Non-Small-Cell Lung Cancer

“…If the patient is overweight or obese (BMI ≥ 25), an adjusted body weight (ABW) should be used. 12,13 Although a number of different formulae for calculating ABW are available, the most commonly used formula is: ABW = [(Actual Body Weight -Ideal Body Weight) (0.4)] + Ideal Body Weight. Ideal Body Weight (IBW) is most commonly calculated as 14 : IBW = 50 kg + 2.3 kg/inch > 60 inch (Men); IBW = 45.5 kg + 2.3 kg/inch > 60 inch (Women).…”

Carboplatin Dosing in Children: Calculation by Different Formulae

“…Thequestionofanadequateweightdescriptorinequations including weight to estimate the carboplatin dose in overweightorobesepatientswithnormalrenalfunctionshouldbe addressednotonlyinadults [26]butalsoinchildren. Thecalculationsforpatientsofabnormalbodybuilddone inthisstudy,whilepossiblyusefulasanindicativetool,areof uncertain predictivity in the individual patient; in high-risk patients,anexactmeasureoftheGFRisessentialandshould becomplementedbytherapeuticdrugmonitoring.…”