Evaluation of the Modified Diet in Renal Disease equation for calculation of carboplatin dose.
BACKGROUND
Serum creatinine (SCr)-based formulas are used to estimate glomerular filtration rate (GFR) when calculating a dosage for carboplatin using the Calvert equation, but these formulas often underestimate measured GFR. The Modified Diet in Renal Disease (MDRD) equation appears to be a more accurate estimate of GFR in patients with chronic kidney disease, but this equation has not been studied extensively in patients with cancer.


OBJECTIVE
To determine the absolute difference between the dose of carboplatin administered (traditional SCr-based formulas used to estimate GFR) and the dose calculated using the MDRD equation to estimate GFR and compare the frequencies of thrombocytopenia, neutropenia, and dosage modifications between subjects in whom the difference in dose was 20% or more (divergent) or less than 20% (nondivergent).


METHODS
A retrospective analysis was conducted using data from patients who received carboplatin. Inclusion criteria were receipt of at least 2 doses of carboplatin, either as monotherapy or combination therapy, and documentation of desired area under the concentration-time curve (AUC). Patients were excluded if the baseline values needed to estimate GFR using the MDRD equation were not available. The absolute difference between the dose of carboplatin administered and that calculated using the MDRD equation was determined and, from this comparison, the subjects were divided into 2 groups (divergent vs nondivergent).


RESULTS
The medical records of 186 adults who received more than 2 doses of carboplatin were included in the analysis. The doses were divergent in 89 (48%) patients. The mean target AUC values were 5.3 mg/mL/min and 5.1 mg/mL/min in the divergent and nondivergent groups, respectively, and most patients received cytotoxic regimens with a relatively low risk of febrile neutropenia. The frequencies of neutropenia, thrombocytopenia, and dosage modifications were similar between the 2 groups. Use of the MDRD equation to calculate the carboplatin dosage did not appear to result in a change in the frequency of myelosuppression or the need for dose modifications compared with traditional SCr-based formulas.


CONCLUSIONS
The traditional SCr-based formulas for the calculation of carboplatin dosage should be used to estimate carboplatin dose until more data become available regarding the use of the MDRD equation in this population.
Shord
Stacy S
SS
College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. sshord@uic.edu
Bressler
Linda R
LR
Radhakrishnan
Latha
L
Chen
Ningyu
N
Villano
J Lee
JL
D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D054796:Drug Dosage Calculations; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count; D012189:Retrospective Studies
D016190:Carboplatin