Luke McLean1, James R Whittle1, Jonathan Graham1, Huda Ismail2, Meir Lichtenstein3, Rodney J Hicks4, Orla McNally5, Alan Herschtal6, Mark Rosenthal7, Danny Rischin7, Anne Hamilton8. 1. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 3000. 2. Royal Womens Hospital, Parkville, Victoria, Australia 3052. 3. Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; The University of Melbourne, Parkville, Victoria 3010, Australia. 4. The University of Melbourne, Parkville, Victoria 3010, Australia; Cancer Imaging, The Peter MacCallum Cancer Centre, Melbourne, Victoria 300, Australia. 5. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 3000; Royal Womens Hospital, Parkville, Victoria, Australia 3052; The University of Melbourne, Parkville, Victoria 3010, Australia. 6. Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre Melbourne, Victoria 3000, Australia. 7. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 3000; The University of Melbourne, Parkville, Victoria 3010, Australia. 8. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia 3000; Royal Womens Hospital, Parkville, Victoria, Australia 3052; Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: anne.hamilton@petermac.org.
Abstract
BACKGROUND: Glomerular filtration rate (GFR) measured by Chromium-51-EDTA excretion (51Cr-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 51Cr-GFR assessment for malignant or non-malignant indications, with a matched CG-GFR. Carboplatin dose based on 51Cr-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: 51Cr-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 51Cr-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 51Cr-GFR, and AUC6 carboplatin based on CG-GFR as equivalent is invalid and should be abandoned. When 51Cr-GFR is unavailable, capping CG-GFR at 125 mL/min is recommended.
BACKGROUND: Glomerular filtration rate (GFR) measured by Chromium-51-EDTA excretion (51Cr-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 51Cr-GFR assessment for malignant or non-malignant indications, with a matched CG-GFR. Carboplatin dose based on 51Cr-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: 51Cr-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 51Cr-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 51Cr-GFR, and AUC6 carboplatin based on CG-GFR as equivalent is invalid and should be abandoned. When 51Cr-GFR is unavailable, capping CG-GFR at 125 mL/min is recommended.
Authors: Edward H Williams; Thomas R Flint; Claire M Connell; Daniel Giglio; Hassal Lee; Taehoon Ha; Eva Gablenz; Nicholas J Bird; James M J Weaver; Harry Potts; Cameron T Whitley; Michael A Bookman; Andy G Lynch; Hannah V Meyer; Simon Tavaré; Tobias Janowitz Journal: Clin Cancer Res Date: 2020-12-10 Impact factor: 13.801
Authors: A Samani; R Bennett; K Eremeishvili; F Kalofonou; S Whear; A Montes; R Kristeleit; J Krell; I McNeish; S Ghosh; L Tookman Journal: ESMO Open Date: 2022-02-26