Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.
BACKGROUND
Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing.


METHODS
We studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable.


RESULTS
115 patients were identified. Mean isotopic GFR was 96.9 ml/min/1.73 m(2). CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose.


CONCLUSIONS
Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential.
['Shepherd|Scott T C|ST|', 'Gillen|Gerry|G|', 'Morrison|Paula|P|', 'Forte|Carla|C|', 'Macpherson|Iain R|IR|', 'White|Jeff D|JD|', 'Mark|Patrick B|PB|']
D000328:Adult D000970:Antineoplastic Agents D019540:Area Under Curve D015992:Body Mass Index D001830:Body Surface Area D016190:Carboplatin D002614:Chelating Agents D004305:Dose-Response Relationship, Drug D004492:Edetic Acid D005919:Glomerular Filtration Rate D006801:Humans D008297:Male D008875:Middle Aged D009367:Neoplasm Staging D051436:Renal Insufficiency, Chronic D018239:Seminoma D013736:Testicular Neoplasms
Formula Glomerular filtration rate Carboplatin Dosing Seminoma