Implications on chemotherapy dose selection of the 4-variable Modification of Diet in Renal Disease equation (MDRD) for estimating renal function

Abstract

2553 Background: Cockcroft and Gault equation (CG) has been utilised for estimating renal function (RF) in cancer patients. MDRD (Ann Intern Med 2006; 145: 247–254) has been recently advocated as the routine method of estimating RF from serum creatinine, however it was developed in patients with chronic renal disease. The aim was to determine concordance of dose selection between CG and MDRD for renally excreted chemotherapy drugs. Methods: This retrospective study was conducted utilising data from hospitalised patients undergoing pharmacokinetic drug dose monitoring at a single institution. CG was calculated using actual body weight. Serum creatinine (SeCr) was measured using Jaffe method and rounded up to 0.06mmol/L. Comparison was made with MDRD adjusted for patient body surface area. Impact on drug dosing was assessed through examination of concordance across renal function ranges utilised in practice for dose selection (<30mL/min, 30–49mL/min, ≥50mL/min). Results: 4,123 patients were included; 62% male; mean age 52.5yrs (range: 18–96yrs), weight 76.8kg (range: 28.9–245kg), height 174.9cm (range: 137–198cm), SrCr 0.085mmol/L (range: 0.06–0.98mmol/L). Mean creatinine clearance (CrCl) was 107.5mL/min (range: 5.7–362mL/min) using CG and mean GFR was 103.9mL (range: 4.7–173mL/min) using MDRD. Concordance between CG and MDRD, adjusted for patient body surface area, is shown in Table 1. Clinical application of MDRD rather than CG would result in 1 in 70 patients receiving a higher dose of chemotherapy and 1 in 200 a lesser dose. Concordance was less with increasing body mass index (BMI) and incorporation of ideal body weight (IBW) in CG. Gender did not influence concordance. Conclusions: There was a high level of concordance in chemotherapy dose selection using MDRD or CG. Impact on dose selection is greater for obese patients and when IBW is utilised in CG. Concordance between CG and MDRD for dose selection of renally excreted chemotherapy MDRD <30ml/min ≥30–49.9mls/min ≥50mls/min CG <30ml/min 72 pts (1.7%) 61 pts (1.5%) 3 pts (0.1%) ≥30–49.9 mls/min 19 pts (0.5%) 213 pts (5.2%) 208 pts (5.0%) ≥50mls/min 0 pts (0%) 71 pts (1.7%) 3,476 pts (84.3%) No significant financial relationships to disclose.