A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients.
OBJECTIVE
It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), actual body weight (ABW), age, and sex. This multicenter pharmacokinetic study was done to evaluate prospectively the benefit of using cysC for carboplatin individual dosing.


METHODS
The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was done using NONMEM program. Seven covariates studied were as follows: Scr, cysC, age, sex, ABW, ideal body weight, and lean body mass.


RESULTS
The best covariate equation was as follows: carboplatin clearance (mL/min) = 117.8. (Scr/75)(-0.450). (cysC/1,00)(-0.385). (ABW/65)(+0.504). (age/56)(-0.366). 0.847(sex), with Scr in micromol/L, cysC in mg/L, ABW in kilograms, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +1% and 15%, respectively, on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index.


CONCLUSIONS
For the first time, a unique formula is proposed for carboplatin individual dosing to patients, which is shown to be equally valid for underweight, normal weight, and obese patients.
Schmitt
Antonin
A
Institut Claudius-Regaud and EA3035 University of Toulouse, Toulouse, France.
Gladieff
Laurence
L
Lansiaux
Amélie
A
Bobin-Dubigeon
Christine
C
Etienne-Grimaldi
Marie-Christine
MC
Boisdron-Celle
Michèle
M
Serre-Debauvais
Françoise
F
Pinguet
Frédéric
F
Floquet
Anne
A
Billaud
Eliane
E
Le Guellec
Chantal
C
Penel
Nicolas
N
Campone
Mario
M
Largillier
Rémy
R
Capitain
Olivier
O
Fabbro
Michel
M
Houede
Nadine
N
Medioni
Jacques
J
Bougnoux
Philippe
P
Lochon
Isabelle
I
Chatelut
Etienne
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055316:Cystatin C / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D011446:Prospective Studies; D015203:Reproducibility of Results; D014018:Tissue Distribution; D055815:Young Adult
D000970:Antineoplastic Agents; D055316:Cystatin C; D016190:Carboplatin