Predicted and measured carboplatin clearance were used to calculate predicted and measured drug exposure by means of the area under the concentration time curve (AUC). 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. Simultaneous determination of intact cisplatin and its metabolite monohydrated cisplatin in human plasma. Flat Dosing of carboplatin is justified in adult patients with normal renal function. The https:// ensures that you are connecting to the found a relatively stable extra-renal clearance of carboplatin equivalent to about 25 mL/min in adults [4]. and E.d.B. Her measured serum creatinine is 1.2 mg/dl. GFR calculator. Furthermore, what should the clinician do when treating a patient outside of a clinical study? 2009 Jun;64(1):115-22. doi: 10.1007/s00280-008-0856-x. Conceptualization, H.N.B., A.B. Leion F., Hegbrant J., den Bakker E., Jonsson M., Abrahamson M., Nyman U., Bjrk J., Lindstrm V., Larsson A., Bkenkamp A., et al. 8600 Rockville Pike All patients had normal renal function, defined as creatinine and cystatin C levels below the age-appropriate upper limit. Estimating glomerular filtration rate (GFR) in children. Ekhart C., De Jonge M.E., Huitema A.D.R., Schellens J.H.M., Rodenhuis S., Beijnen J.H. Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. Renal function-based dosing is of particular importance in children as it corrects for changes in renal function during childhood [14], but has not yet been implemented in standard clinical practice. If the patient's weight changes by 10% or more, the carboplatin dose will need to be recalculated. This calculator calculates carboplatin doses via the Calvert formula with a target Area Under the Curve (AUC), using three options for kidney function: Directly Measured GFR (mGFR)* Body Surface Area (BSA) Adjusted eGFR CKD-EPI ** Creatinine Clearance (CrCl) calculated via the Cockcroft-Gault equation If radiopharmaceutical clearance is not used to measure GFR, creatinine clearance (CrCl) estimated by the Cockcroft-Gault method 14 is commonly used to estimate GFR. Creatinine clearance (CrCl) can be determined using the Cockcroft-Gault Equation: $$ CrCl \ (males) = { (140 - age \ in \ years) \times Weight \ (kg) \over 72 \times Serum \ creatinine ({mg \over dl})}$$. government site. The volume of distribution was allometrically scaled to corrected lean body mass. Calvert formula Carboplatin dose = AUC (GFR + 25). In the total group as well as the two subgroups, the Schwartzcys equation performed best both in terms of bias and accuracy. National Kidney Foundation. Creatinine clearance (Ccr) is widely used as a practical substitute for glomerular filtration rate (GFR) in the Calvert formula . To minimize the burden for outpatients, a limited sampling strategy with two samples (1.5 and 5 h after start of infusion) was applied in three patients in four studies. The population that is at greatest risk for an overdose is the group of patients with normal renal function, especially since there is little evidence of the value of AUC formulas to estimate dosing. Patients received an intravenous carboplatin dose of 560 mg/m2 (in children 10 kg) or 18.7 mg/kg (in children <10 kg) during one hour. These formulas typically include creatinine level, age, weight, and sex (Table 1). 2. 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. Prediction of creatinine clearance from serum creatinine. Generally, glomerular filtration rate (GFR) is estimated using serum creatinine and calculated according to the Cockcroft-Gault equation. Ma J., Stoter G., Verweij J., Schellens J.H.M. In Figure 2, %PE in anthropometric dosing appears to be directly related to body weight, leading to significant underdosing in the youngest children, while %PE is mostly positive in studies above 10 kg. Approach: : Calculate her ABW and IBW, and use the Cockcroft-Gault equation to calculate her creatinine clearance, $$ CrCl \ (females) = { (140 - 60) \times 57 \over 72 \times 1.2} \times 0.85$$. After visual inspection of the concentrationtime curves there was an adequate goodness of fit of the final model and no bias was observed. Therefore, taking the patients kidney function into account to calculate the adequate dose of carboplatin might result in a better exposure of carboplatin within a patient. Therefore, weight-based dosing will result in lower carboplatin exposure in small children, as observed here. Carboplatin was administered intravenously for 60 min at a constant rate, diluted in 5% dextrose at doses ranging from 80 mg to 430 mg (median 340 mg) via central venous catheters. Therefore, the creatinine clearance is 0.67mL/ min. Disclaimer, National Library of Medicine Purpose: The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance. and G.J.P. Janowitz T., Williams E.H., Marshall A., Ainsworth N., Thomas P., Sammut S.J., Shepherd S., White J., Mark P., Lynch A., et al. Diagnostic graphs and additional statistical analyses were made using IBM SPSS statistics 22 (Chicago, IL, USA) and GraphPad Prism 7.0 (San Diego, CA, USA). Estimated Clearance Equations Cockcroft and Gault equation: Male: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Female: Multiply above result by 0.85 Reference: Cockcroft DW, Gault MH. The authors declare no conflict of interest. The myelotoxicity and clinical efficacy of carboplatin correlate with the clearance of the drug, which is correlated to the glomerular filtration rate (GFR). This formula is called the creatinine clearance and tends to exceed the true GFR by 10 to 20 percent or more depending upon the proportion of urinary creatinine that is derived from tubular secretion [ 4 ]. Calvert A.H., Newell D.R., A Gumbrell L., OReilly S., Burnell M., E Boxall F., Siddik Z.H., Judson I.R., E Gore M., Wiltshaw E. Carboplatin dosage: Prospective evaluation of a simple formula based on renal function. Carboplatin dose (mg) = AUCx (GFR + 25) Carboplatin dose (mg) = 7 x (81.25 + 25) Carboplatin dose (mg) = 7 x 106.25 Carboplatin dose (mg) = 743.8 The carboplatin calculator can be used to find the exact dosage for patients of various age groups. The creatinine clearance used to calculate the carboplatin dose will be from PHYS 75 at Emory University 2017 Oct 18;4:15. doi: 10.1186/s40661-017-0054-9. Observed carboplatin clearance ranged from 11.68 mL/min to 57 mL/min (median 33.42 mL/min), and observed AUC ranged from 3.56 mg/mL.min to 12.81 mg/mL.min (median 7.29 mg/mL.min). 1988;21(2):163-7 US Food & Drug Administration. Second, the GFR in our patients was normal, which may have reduced the potential benefit of kidney function-based dosing when compared to anthropometric dosing. The dotted lines indicate the thresholds of +25% and 10%, also used for the calculation of accuracy (10 to 25%). Therefore, it is assumed there is limited additional value of adding urea in an equation for this specific population. The concern we face is that the historical approach has primarily relied on the creatinine measurement in the estimation of renal func- tion. 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. For patients with abnormal renal function, the usual formulas are less likely to be problematic. Binary performance outcome of the different eGFR equations were compared using the McNemar test, Chi-squared test or Fishers exact test. Historically, this error was balanced by an error of almost equal magnitude in the measurement of the serum creatinine. This has been studied extensively in adults [18,19]. In Figure 1, %PE of the different eGFR equations and anthropometric dosing in the individual studies is shown as waterfall plots. These numbers are roughly interpolated from the information provided at the . Plasma free platinum pharma-cokinetics in patients treated with high dose carboplatin. As illustrated by Beumer et al. Blufpand H.N., Tromp J., Abbink F.C., Stoffel-Wagner B., Bouman A.A., Meeteren A.Y.S.-V., van Wijk J.A., Kaspers G.J., Bkenkamp A. Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. 2022 Jul 19;24(3):583. doi: 10.3892/etm.2022.11520. Unlike the other commonly used formulas (eg, Cockroft-Gault, Jelliffe), it is based on the new creatinine assay. The site is secure. and Creatinine clearance (CrCl) values range from 1.24-2.24 mL/second. Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient. - The estimated creatinine clearance rate (eCCr): 70.73 ml/min - The estimated ideal body weight: 181.23 lbs or 82.20 kg. Briefly, a two-compartment model was developed with first-order elimination which describes carboplatin concentrationtime profiles: clearance was 8.38 L/h; volume of distribution was 15.4 L and the distribution micro-constants k12 and k21 were 0.135 h-1 and 0.215 h-1, respectively. 8600 Rockville Pike 1998;42(4):307-12. doi: 10.1007/s002800050822. Epub 2008 Nov 7. The https:// ensures that you are connecting to the Veal et al. Go R.S., Adjei A.A. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. Prospective validation of renal functionbased carboplatin dosing in children with cancer: A United Kingdom childrens cancer study group trial. Estimated Clearance Equations Cockcroft and Gault equation: Male: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Female: Multiply above result by 0.85 Reference: Cockcroft DW, Gault MH. A decreased renal (kidney) function would Cockcroft-Gault equation takes into account the age of the patient as well, since muscle mass decreases with age. Clipboard, Search History, and several other advanced features are temporarily unavailable. GFR = glomerular filtration rate, CL cr = creatinine clearance, TBW . Appropriate patient weight and serum creatinine should be used . The dotted lines indicate the thresholds of percentage error of +25% and 10%. Disclaimer, National Library of Medicine Unable to load your collection due to an error, Unable to load your delegates due to an error. It should be borne in mind that the Calvert equation and, by extension, the Newell equation, are based on measured GFR in mL/min. This is remarkable as both Schwartzcys and FAScys were developed in children above the age of one [29,42], while the youngest patient in the cohort of Brandt et al. In children, a number of eGFR equations have been developed using either creatinine and/or cystatin C [ 20 ]. Dose modification . -, Ann Oncol. and G.L.K. However, although the CKiD-3 equation is very accurate for eGFR measurements, it is not feasible in this population since carboplatin administration is always combined with hyperhydration, which strongly affects urea concentrations [48]. ; supervision, A.B., G.J.P. and transmitted securely. These were deemed the optimal timepoints to cover the expected distributionelimination curve. Bookshelf It is most commonly used to treat lung and ovarian cancers, but has been used off-label in many other diseases. Giaccone G., Gonzlez-Larriba J.L., van Oosterom A.T., Alfonso R., Smit E.F., Martens M., Peters G.J., van der Vijgh W.J.F., Smith R., Averbuch S., et al. Nephron. MeSH Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae. Bouquegneau A, Vidal-Petiot E, Moranne O, Mariat C, Boffa JJ, Vrtovsnik F, Scheen AJ, Krzesinski JM, Flamant M, Delanaye P. Br J Clin Pharmacol. 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. Mosteller R.D. Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C. Berg U.B., Nyman U., Bck R., Hansson M., Monemi K., Herthelius M., Bjrk J. Unfortunately, no one knows the answer to these questions because of the uncertainty over carboplatin dosing. IBW is used based on the rationale that creatinine comes from lean muscle, so IBW would give a closer estimation of creatinine clearance. The different dosing equations were developed using gold standard GFR measurements (i.e., 51Chromium ethylenediamine tetraacetic acid (51Cr-EDTA) clearance and technetium-99 m diethylenetriaminepentacetic acid (99mTc-DTPA) clearance). HHS Vulnerability Disclosure, Help Zorbas Y.G., Ichinose M.N., Sakagamis M.B. 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]. The most frequently used measure of kidney function is creatinine clearance. 2010 Nov 29. The percentage prediction error (%PE), defined as: The absolute percentage prediction error (APE), Accuracy assessed by calculating the proportion of predicted AUC values within 30% of measured AUC (P. Received 2021 Oct 8; Accepted 2021 Nov 19. ); ln.cmumadretsma@pmaknekob.a (A.B. Epub 2018 Oct 18. Fourth, calculation of the observed carboplatin AUC was based on the publication by Ekhart et al. Geurtsen M.L., Kors W.A., Moll A.C., Smits C. Long-term audiologic follow-up of carboplatin-treated children with retinoblastoma. For this, the standard pharmacokinetic formula [dose = clearance carboplatin x target AUC] is used. Actual doses were calculated based on the Cockcroft-Gault formula with total body weight. Simplified calculation of body-surface area. Currently, there is not much evidence for its utility in the context of car- boplatin dosing. 2. The patient has a creatinine clearance of 44.9 ml/min, so based on the dosing chart provided her dose would be 4 g IV q6h . Int J Prev Med. These different eGFR equations might be used instead of a gold standard GFR measurement in the widely used Newell equation to calculate carboplatin clearance [6]. -. Given the physiological differences in body dimensions and renal function [20] between young infants and older children, we analyzed patients under two years separately from older children. and E.d.B. In renally-impaired patients who received single agent Carboplatin Injection therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have . Epub 2016 Jan 17. 1 Original Cockcroft-Gault equation: CrCl = (140age)(weight in kg) (0.85, if female) 72*SCr Percentage prediction error (%PE) of the different dosing methods. Measured carboplatin clearance obtained from these individual fits were compared with predicted carboplatin clearance using the Newell equation [6]: As most eGFR equations yield standardized GFR in mL/min/1.73 m2 GFR was converted to absolute GFR in mL/min before use in the Newell formula. ); ln.cmumadretsma@sretep.jg (G.J.P. Qualitative variables are displayed as numbers (%). Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors. Combining a cystatin C- and a creatinine-based eGFR yielded similar results. When to Use Pearls/Pitfalls Why Use Sex Female Male Age years Weight lbs Creatinine mg/dL To be eligible for study participation, patients had to be between 0 and 18 years old and scheduled to receive carboplatin for the treatment of retinoblastoma. Nephron 1976;16 (1):31-41. Cockcroft DW, Gault MH. An aliquot of plasma (0.5 mL) was thoroughly mixed with 1.5 mL of ice cold (20 C) ethanol and incubated for several hours at 20 C to denaturize the plasma proteins. and G.J.P. Still, none of the patients here showed hyperfiltration as all eGFR measurements were below 140 mL/min/1.73 m2. PMC Okamoto H, Nagatomo A, Kunitoh H, Kunikane H, Watanabe K. Cancer Chemother Pharmacol. the display of certain parts of an article in other eReaders. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The target AUC of carboplatin used in this study was 7.42 mg/mL.min and was based on previously published data by Newell et al [6]. This dosing calculator adjusts for renal . This carboplatin dosing calculator uses the Calvert method to calculate the total carboplatin dose needed to achieve a given AUC (area under the free carboplatin plasma concentration versus time curve) while taking into account renal function. This method, however, underestimates serum creatinine values compared to previous approaches when serum creatinine values are low, at approximately 0.7 mg/dL. Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children. However, the only study so far evaluating eGFR for carboplatin dosing in pediatric oncology patients compared eGFR with a gold standard GFR measurement and extrapolated these findings to drug exposure [15]. However, gold standard GFR measurements using inulin, 51Cr-EDTA, 99Tc-DTPA, 125I-iothalamate or iohexol [14,36,37] are invasive, costly and cumbersome, thereby precluding widespread use in clinical practice. Pironi L., Delanaye P., Boutten A., Bargnoux A.-S., Rozet E., Delatour V., Carlier M.-C., Hanser A.-M., Cavalier E., Froissart M., et al. Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer. Ekhart C., Rodenhuis S., Schellens J.H.M., Beijnen J.H., Huitema A.D.R. 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). In our study, however, neither of these two equations performed better than the general Schwartzcrea equation and had higher %PE values than Schwartzcys, indicating overestimation of GFR. Study objectives: Improving carboplatin dosing based on estimated GFR. Oncologist. Solved Problem: Calculate the creatinine clearance of a 60-year-old, 140 lb, 55 female? The equation is: carboplatin dose (mg) = AUC x [GFR + 25]. Formula to calculate creatinine clearance. A lot of the variability in calculating the carboplatin dose is due to physicians utilizing results of serum creatinine tests to estimate the glomerular filtration rate (GFR), as based on one of various formulas, many of which have not been sufficiently prospectively evaluated. Abstract. . After the sampling procedure, all samples were immediately placed in an ice bath and centrifuged (1500 g at 4 C for 10 min), to separate plasma from whole blood. Schwartz G.J., Schneider M.F., Maier P.S., Moxey-Mims M., Dharnidharka V.R., Warady B.A., Furth S.L., Muoz A. ; visualization, M.E.v.d.V. Residual error was assumed to be distributed normally with a standard deviation according to SD = 0.1 C, in which C is platinum plasma concentration. ); ln.murtnecamixamsesnirp@srepsak.ljg (G.L.K. Different studies employ different formulas or approaches to carboplatin dosing. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of Amsterdam UMC, location VUmc (formerly known as VUmc) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Stardew Valley Craftable Recolor, Bts Albums In Order 2013 To 2022, Conda Activate Environment From Path, Workplace Situations Examples, Detective Conan Criminal Figure, Nora Symbolism In A Doll's House, Restaurants Near Sse Arena Belfast, Extensive Horsts Crossword Clue, Cd Arenteiro Vs Real Aviles, Greenstake Biodegradable Stakes,