Carboplatin dosing in the era of IDMS-creatinine; the Cockroft-Gault formula no longer provides a sufficiently accurate estimate of glomerular filtration rate for routine use in clinical care.

BACKGROUND: Glomerular filtration rate (GFR) measured by Chromium-51-EDTA excretion (51 Cr-GFR) is considered the gold standard of renal function assessment, but serum creatinine in the Cockcroft-Gault (CG) formula is routinely used to estimate GFR for carboplatin dosing. Serum creatinine measured by isotope-dilution-mass-spectrometry (IDMS) can generate spuriously high GFR estimates when used in the CG formula. We hypothesized that GFR calculated using IDMS-creatinine in the CG formula (CG-GFR) exposes patients to inaccurate carboplatin dosing.

METHODS: This is a multicenter retrospective study of patients who had a 51 Cr-GFR assessment for malignant or non-malignant indications, with a matched CG-GFR. Carboplatin dose based on 51 Cr-GFR at AUC5 was used as the reference.

RESULTS: 550 patients were analyzed, median age 62 (19-90), 64% female. Indication for GFR evaluation: malignancy (85%), assessment for live kidney donation (12%), other (3%). Median ratio of CG-GFR: 51 Cr-GFR 1.04 (0.43-3.38); <0.8 in 72 patients (13%), >1.2 in 180 patients (33%). Despite capping of CG-GFR at 125 mL/min, dosing according to AUC6 would have resulted in 18% of patients being underdosed and 23% overdosed by >100 mg compared to 51 Cr-GFR. Subgroup analysis identified BMI (>35, MPE 39%), gender (female MPE 15%), GFR indication (malignancy MPE 11%) as risk factors for overestimate of CG-GFR, and BMI < 20 for underestimate (MPE -3.5%).

CONCLUSIONS: The convention of considering AUC5 carboplatin based on 51 Cr-GFR, and AUC6 carboplatin based on CG-GFR as equivalent is invalid and should be abandoned. When 51 Cr-GFR is unavailable, capping CG-GFR at 125 mL/min is recommended.