The effect of Cockcroft-Gault (CG) measurement of GFR on carboplatin dosage in ovarian cancer patients compared with Cr51-EDTA.

Abstract

e15538 Background: The accepted gold standard for carboplatin dose calculation is the Calvert formula: Dose = (GFR + 25) x AUC. GFR (glomerular filtration rate) calculation is commonly made with formulae such as CG, which are based on serum creatinine. Cr51-EDTA, a radionuclide scan, also can be used to calculate GFR and is more accurate with closest estimation to inulin clearance (gold standard for GFR). The impact of factors such as body mass index (BMI), muscle mass and serum albumin upon the accuracy of CG versus EDTA is not well-defined. Many international clinical trials correct the AUC to a higher level when CG formula is applied. Methods: Identification of patients from local gynaecology-oncology database undergoing carboplatin-based chemotherapy for ovarian cancer, all of whom had Cr51-EDTA between January 2008 and January 2011. Evaluation of BMI, serum albumin, serum creatinine and disease status prior to chemotherapy. Comparison of theoretical Carboplatin doses based on Cr51-EDTA versus CG formula, termed Dose-EDTA and Dose-CG respectively. Results: 58 patients,mean age 61 years (range 31-81), mean BMI 27.8 (17.95-48.01). Mean albumin 40g/L (25-50) and mean serum creatinine 66umol/L (35-139). Carboplatin dose-CG exactly matched Dose-EDTA in only 1 patient (1.7%) and over-estimated carboplatin dose in 49 patients (84.5%), with over-estimation by ≥10% in 63.7% and ≥30% in 32.7%. Dose-CG underestimated carboplatin dose in 13.8%, with underestimation by ≥10% in 5.2%. Bland-Altman analysis showed that over-estimation of Dose-CG increased as the average dose increased. Multifactorial analysis is underway to identify patients at higher risk of over-estimated Dose-CG and will be presented at meeting. Conclusions: Carboplatin dosing based on CG measurement is frequently inaccurate and significantly overestimates the dose compared to Cr51-EDTA. The practice of increasing the AUC by one level when using CG will lead to significant overdosage of carboplatin in most ovarian cancer patients and should not be applied. Where facilities are available, consideration should be given to routine use of Cr51-EDTA to calculate carboplatin dosage.