and G.L.K. In this study, the CKD-EPI equation was found to have better performance than the MDRD equation; however, further research is needed to determine if widespread use of CKD-EPI is appropriate. Stage 3 ckd, a . Although largely eliminated renally, roughly 20% of carboplatin is non-renally cleared, which to a large extent is due to tissue binding, with a small proportion excreted through the liver [11,44]. Her measured serum creatinine is 1.2 mg/dl. Prediction of total body water in infants and children. Measuring serum creatinine Historically - colorimetric 'Jaffe' method used. This formula has proven to be, in both retrospective and prospective studies, a reliable tool to calculate the optimal dose of carboplatin Future studies should determine the value of the creatinine clearance as a measure for the GFR. Unlike the other commonly used formulas (eg, Cockroft-Gault, Jelliffe), it is based on the new creatinine assay. Results We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. This indicates that an individual dosing strategy is warranted to obtain the optimal AUC. The use of the Calvert formula to calculate carboplatin doses allows clinicians to achieve the appropriate carboplatin area under the concentration (AUC) curve. The original study published in 1976 used actual body weight, but it mentioned that a correction factor was likely needed for those who are obese. The linear relationship between carboplatin clearance and glomerular filtration rate (GFR) initiated the development of carboplatin dosing equations based on renal function in adults [4] as well as children [6,7]. 1984 Feb;4(1):61-74 Nephron. The .gov means its official. 3. Epub 2012 May 10. These were deemed the optimal timepoints to cover the expected distributionelimination curve. H&O What are the new changes in serum creatinine, and how might they affect carboplatin dosing? 2007;12:913-923. [46] in their commentary on a recently published new model for GFR estimation in adults [47], each conversion step, i.e., from measured GFR to estimated GFR [20] and also from GFR in mL/min to GFR in mL/min/1.73 m2 introduces the potential for bias. Carboplatin dosing using eGFR may therefore be a more practical alternative to calculate the appropriate carboplatin dose. The United Kingdom Childrens Cancer Study Group. Glomerular filtration rate measurement and estimation in chronic kidney disease. and Creatinine clearance (CrCl) values range from 1.24-2.24 mL/second. Since the local standard retinoblastoma treatment protocol used anthropometric dosing based on BSA for children over 10 kg and on body weight for smaller children to achieve a carboplatin exposure within the target AUC, this approach was evaluated by comparing target AUC and measured AUC using the parameters described above (%PE, APE and accuracy). eCollection 2017. government site. Carboplatin dosing. As the area under the concentration-time curve (AUC) of free carboplatin is related with efficacy and toxicity following carboplatin administration, carboplatin dosing is defined as a. Carboplatin is a chemotherapeutic agent that is usually dosed based on body surface area or weight. Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. and G.L.K. Prediction of creatinine clearance from serum creatinine. In addition, for this equation, cancelling the units does not work, so this equation is an exception to the rule that units should cancel out. After visual inspection of the concentrationtime curves there was an adequate goodness of fit of the final model and no bias was observed. We acknowledge a number of limitations in our study. Clin J Am Soc Nephrol. 2013 Jul-Aug;47(7-8):1039-44. doi: 10.1345/aph.1S176. Concomitant chemotherapeutic drugs were vincristine 1.5 mg/m2 and etoposide 150 mg/m2, administration of which are part of the local standard treatment protocol. Dosing of this agent based solely upon the patients body surface area is therefore not accurate enough; the GFR, and thus the clearance of carboplatin differ in each patient irrespective of the body area. Currently, there is not much evidence for its utility in the context of car- boplatin dosing. A large simulation study compared eGFR by MDRD Study equation and estimated creatinine clearance (eCrCl) by the Cockcroft-Gault equation calculated from standardized creatinine values to each other and to measured GFR for the purpose of drug dosing. MR It is necessary to establish a consistent approach to estimating creatinine clearance so that we can reduce vari- ability across institutions and translate clinical trial results into clinical practice. As a temporary measure, it has been suggested that physicians limit the dose of car- boplatin in order to avoid overdosing if they are using the IDMS method to measure serum creatinine. 2022 Jul 19;24(3):583. doi: 10.3892/etm.2022.11520. Mirjam E. van de Velde, Emil den Bakker, [], and Arend Bkenkamp. You multiply the result by 0.85 to get creatinine clearance for a woman. Of note, the difference in eGFR between both age groups was highest for the Berg equation and lowest for the Schwartzcrea equation. The choice of sampling points was based on population PK modeling and on sampling points described earlier in the literature for carboplatin [5,6,21]. 2017 Feb;56(2):193-205. doi: 10.1007/s40262-016-0434-z. Of note, only four infants participated in the development of the Newell equation [6]. 2012 Jul;32(7):604-12. doi: 10.1002/j.1875-9114.2012.01098.x. Body surface area (BSA) was calculated according to Mosteller [35]. To ensure patient safety and facilitate a medical-team approach, the single most appropriate method available at each institute or medical team should be consistently used to calculate the dose of carboplatin . Different dosing regimens were compared in terms of accuracy, bias and precision. already built in. Continuous variables are presented as median (interquartile range; IQR). The performance of this analytical procedure was comparable to the original assays [23,24,25], regarding linearity (linear in the range of the used calibration line of 2.540 M carboplatin), lower limit of quantitation for total platinum (2.5 M), within and between day accuracy of total platinum (1213%) and unbound platinum (3%). Pottel H., Dubourg L., Schaeffner E., Eriksen B.O., Melsom T., Lamb E.J., Rule A.D., Turner S.T., Glassock R.J., De Souza V., et al. Den Bakker E., Gemke R.J.B.J., Bkenkamp A. Endogenous markers for kidney function in children: A review. Calvert formula Carboplatin dose = AUC (GFR + 25). Formula to calculate creatinine clearance. All but two patients were studied during multiple courses (two during two courses, four during three courses and five during four courses). Chatelut E., Boddy A.V., Peng B., Rubie H., Lavit M., Dezeuze A., Pearson A.D.J., Roch H., Robert A., Newell D.R., et al. INSTRUCTIONS For use in patients with stable renal function to estimate creatinine clearance. ), 2Department of Pediatric Oncology/Hematology, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands, 3Emma Childrens Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Nephrology, 1081 HV Amsterdam, The Netherlands; ln.cmumadretsma@rekkabned.lime (E.d.B. This dosing calculator adjusts for renal . Appropriate patient weight and serum creatinine should be used when estimating GFR for use in the Calvert equation. APE: absolute percentage prediction error, %PE: percentage prediction error. Overall, the extremes of both positive and negative accuracy were less in the cystatin C-based equations. Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients. Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in treatment of newly diagnosed pediatric solid tumors. Siddik Z.H., Newell D.R., Boxall F.E., Harrap K.R. Evaluation of formulas using the serum creatinine level to calculate the optimal dosage of carboplatin. Currently, there is marked uncertainty as to what the correct formula is, but the immediate challenge is to avoid overdosing of patients with apparently normal renal function. The results show that application of the alternate size descriptor adjusted body weight in the Cockcroft-Gault equation can improve dosing accuracy especially in overweight and obese patients with low serum creatinine levels. 2010;36:1-6. http://www.cancerletter.com. In Figure 1, %PE of the different eGFR equations and anthropometric dosing in the individual studies is shown as waterfall plots. Calvert AH, Newell DR, Gumbrell LA, et al. Pharmacokinetics and preliminary clinical data of the novel chemoprotectant BNP7787 and cisplatin and their metabolites. ; formal analysis, M.E.v.d.V. Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. Binary performance outcome of the different eGFR equations were compared using the McNemar test, Chi-squared test or Fishers exact test. and G.J.P. The myelotoxicity and clinical efficacy of carboplatin correlate with the clearance of the drug, which is correlated to the glomerular filtration rate (GFR). H&O Can you provide some background on carboplatin? ; writingreview and editing, M.E.v.d.V., E.d.B., A.B., A.W.A.K., A.J.W., F.C.H.A., G.L.K., B.S.-W. and G.J.P. The cystatin C-based equations performed slightly better than the creatinine-based equations, in particular in younger children. In this study we sought to validate a carboplatin dosing method based on kidney function and compare several methods for kidney function-based carboplatin dosing in children suffering from retinoblastoma. Approach: Use the creatinine clearance value from the above problem, compare it to the dosing chart provided in this problem. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Carboplatin dosing using eGFR may therefore be a more practical alternative to calculate the appropriate carboplatin dose. In this article, the development and application of a simple equation, known as the Calvert formula, are discussed. Discrepancies between the Cockcroft-Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies.
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