This was not observed with any of the eGFR-based dosing methods. All alternate dose calculations were not inferior to the calculation based on Cockcroft-Gault using total body weight. For this, the standard pharmacokinetic formula [dose = clearance carboplatin x target AUC] is used. Riccardi R., Riccardi A., Lasorella A., Di Rocco C., Carelli G., Tornesello A., Servidei T., Iavarone A., Mastrangelo R. Clinical pharmacokinetics of carboplatin in children. Delanaye P, Guerber F, Scheen A, Ellam T, Bouquegneau A, Guergour D, Mariat C, Pottel H. Clin Pharmacokinet. Cockcroft-Gault equation takes into account the age of the patient as well, since muscle mass decreases with age. 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. the display of certain parts of an article in other eReaders. Overestimation may result in divergent carboplatin dosages that correlate with dose-limiting . US Food and Drug Administration. Our results need to be confirmed in a larger cohort, including a larger age spectrum, to determine its clinical relevance. The most commonly used formula was developed by Dr. Calvert and is referred to . [(accessed on 26 November 2021)]; Blufpand H.N., Westland R., van Wijk J.A., Roelandse-Koop E.A., Kaspers G.J., Bkenkamp A. Height-independent estimation of glomerular filtration rate in children: An alternative to the Schwartz equation. All patients had normal eGFR. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Amsterdam UMC location VUmc (formerly known as VU University Medical Center) (protocol code Farmacokinetiek van Carboplatine 2.0, date: 10-02-2011). 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). Creatinine clearance calculator If you need medical care or advice that is urgent but not an immediate, genuine emergency, please visit https://111.nhs.uk/ or call 111 first so that trained NHS 111 advisors can tell you the best place to be seen quickly. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. A weighted mean of 40% eGFRcreat and 60% eGFRcys has been suggested to be optimal for patients with malignancy [43]. Different studies employ different formulas or approaches to carboplatin dosing. and G.J.P. Clin J Am Soc Nephrol. Pottel H., Delanaye P., Schaeffner E., Dubourg L., Eriksen B.O., Melsom T., Lamb E.J., Rule A.D., Turner S.T., Glassock R.J., et al. Wanted: methods to measure or estimate renal function for dosing cancer drugs. New Model for Estimating Glomerular Filtration Rate in Patients With Cancer. formula used to calculate the carboplatin dose based on the target AUC in the chemotherapy order forms. Male = 50 kg + (2.3 * (Height in inches - 60)) Female = 45.5 kg + (2.3 * (Height in inches - 60)) Carboplatin dose based on the Calvert formula is: Dosage = Target AUC x (GFR + 25) Carboplatin and target AUC The carboplatin dosage value is calculated by taking into account the target area concentration versus time curve and estimated GFR. government site. 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. Morrow A, Garland C, Yang F, De Luna M, Herrington JD. of serum creatinine-based GFR estimations, the GFR or creatinine clearance should be directly measured in each patient whenever possible. ; funding acquisition, H.N.B. 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 Thomas H., Boddy A., English M.W., Hobson R., Imeson J., Lewis I., Morland B., Pearson A.D.J., Pinkerton R., Price L., et al. At various time points, venous blood (2 mL) was collected into tubes containing lithium heparin anticoagulant. Jodrell D.I., Egorin M.J., Canetta R.M., Langenberg P., Goldbloom E.P., Burroughs J.N., Goodlow J.L., Tan S., Wiltshaw E. Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. Cancer Therapy Evaluation Program. It should be borne in mind that the Calvert equation and, by extension, the Newell equation, are based on measured GFR in mL/min. Calculation of carboplatin clearance may be more accurate by using other weight descriptors such as Epub 2012 May 10. Appropriate patient weight and serum creatinine should be used . and G.L.K. H&O What are the concerns associated with carboplatin dosing? All hospitals used the Calvert formula to calculate carboplatin dose with glomerular filtration rate estimated by a formula, most commonly the Cockcroft-Gault equation (80.7%). This leads to a particular shortcoming in pediatric oncology patients, where muscle wasting from treatment and malignancy may cause inappropriately low creatinine values thereby masking kidney failure. ), 4Princess Mxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands, 5Emma Childrens Hospital, Amsterdam UMC, Amsterdam Medical Center, Pediatric Oncology, 1081 HV Amsterdam, The Netherlands; ln.cmumadretsma@knibba.f, 6Amsterdam UMC, Vrije Universiteit Amsterdam, Clinical Pharmacology and Pharmacy, 1081 HV Amsterdam, The Netherlands; ln.cmumadretsma@mlehliw.ja, 7Laboratory of Medical Oncology, Amsterdam University Medical Center, VUMC, 1081 HV Amsterdam, The Netherlands; ln.cmumadretsma@llewyenoh.r (R.J.H. 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. Bookshelf Therefore, it remains to be demonstrated whether our results can be extrapolated to other populations, in particular to patients with a more diverse range of kidney function, but it is conceivable that differences will be more pronounced in this group of patients. INSTRUCTIONS For use in patients with stable renal function to estimate creatinine clearance. Cockroft-Gault formula [41]. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Workgroup. 2017 Feb;56(2):193-205. doi: 10.1007/s40262-016-0434-z. Combination therapy with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, gemcitabine and cisplatin in patients with advanced solid tumors. Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. The volume of distribution was allometrically scaled to corrected lean body mass. Currently, there is not much evidence for its utility in the context of car- boplatin dosing. Glomerular filtration rate measurement and estimation in chronic kidney disease. 2. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. Creatinine clearance (CrCl) can be determined using the Cockcroft-Gault Equation: $$ CrCl \ (males) = { (140 - age \ in \ years) \times Weight \ (kg) \over 72 \times Serum \ creatinine ({mg \over dl})}$$. Wells J.C.K., Fewtrell M.S., Davies P.S.W., Williams J.E., Coward W.A., Cole T.J. If the patient's weight changes by 10% or more, the carboplatin dose will need to be recalculated. Percentage prediction error (%PE) of the different dosing methods. Thrombocytopenia is the dose limiting toxicity of carboplatin and optimizing AUC minimizes the risk of thrombocytopenia. 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. While performing well in the overall analysis, anthropometric dosing is hampered by a weight-dependent change in bias. Generally, glomerular filtration rate (GFR) is estimated using serum creatinine and calculated according to the Cockcroft-Gault equation. ; writingoriginal draft preparation, M.E.v.d.V., E.d.B., A.B., G.L.K. Approach: Use the creatinine clearance value from the above problem, compare it to the dosing chart provided in this problem. The percentage of body mass is used as follows: Foot 1.35%, at the knee 6.2%, at the hip 18%, hand 0.6%, at elbow 2.25%, at shoulder 5%. Den Bakker E., Gemke R.J.B.J., Bkenkamp A. Endogenous markers for kidney function in children: A review. Calvert measured GFR by clearance of chromium-51-EDTA. Combining GFR estimates from cystatin C and creatininewhat is the optimal mix? All tests were done at a two-sided significance level of 0.05. The additional proximal tubule secretion falsely elevates the CrCl estimate of GFR. The ePub format uses eBook readers, which have several "ease of reading" features Disclaimer, National Library of Medicine This method, however, underestimates serum creatinine values compared to previous approaches when serum creatinine values are low, at approximately 0.7 mg/dL. Unable to load your collection due to an error, Unable to load your delegates due to an error. Measuring serum creatinine with the IDMS method may result in overestimation of the GFR in patients with normal renal function, and if the carbopla- tin dose is calculated based on this method, the dose may result in drug-related toxicities. All but two patients were studied during multiple courses (two during two courses, four during three courses and five during four courses). 1988;21(2):163-7 Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children. Best performed the combination of Cockcroft-Gault with adjusted body weight. This research was funded by Fonds Nuts Ohra, grant number 1302-005. Carboplatin is a chemotherapeutic agent that is usually dosed based on body surface area or weight. 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. -, Ann Oncol. Of note, the difference in eGFR between both age groups was highest for the Berg equation and lowest for the Schwartzcrea equation. and Creatinine clearance (CrCl) values range from 1.24-2.24 mL/second. The United Kingdom Childrens Cancer Study Group. Analysis of carboplatin dosing in patients with a glomerular filtration rate greater than 125mL/min: To cap or not to cap? 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. Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae. It would therefore be useful to recalibrate the Newell equation in children using eGFR instead of measured GFR and also re-evaluate the extra-renal clearance of carboplatin. and G.L.K. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The patient characteristics are summarized in Table 2. Historically, this error was balanced by an error of almost equal magnitude in the measurement of the serum creatinine. Prediction of creatinine clearance from serum creatinine. 8600 Rockville Pike and G.J.P. Carboplatin dosing. Presented at the International Oncology Conference in Kathmandu, Nepal 2014. The dose required to achieve the target AUC is then esti- mated based on one of the available formulas, ideally the one that was studied in the clinical trial that is being used as the basis for the treatment decision. The performance of all six eGFR-based equations as well as anthropometric dosing in predicting carboplatin AUC is presented in Table 3. and E.d.B. Federal government websites often end in .gov or .mil. 4. Capping the GFR (or Clcr) at 125 mL/min, using an adjusted body weight for overweight or obese patients and using a minimum serum creatinine of 0.7 mg/dL as recommended by NCCN to avoid Each symbol indicates the same patients in all figures. Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients. We only included retinoblastoma patients resulting in a very homogenous and young population without much comorbidity. 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. Would you like email updates of new search results? Combining a cystatin C- and a creatinine-based eGFR yielded similar results. The dotted lines indicate the thresholds of +25% and 10%, also used for the calculation of accuracy (10 to 25%). and R.J.H. In the older children, Schwartzcrea, Schwartzcys and Millisor had the least bias and highest precision and yielded high P30 accuracy. The equation is: carboplatin dose (mg) = AUC [GFR + 25]. Percentage prediction error according to weight in all patterns. The authors are indebted to the patients and their parents who participated in the study. An optimal design was calculated based on previously published carboplatin population pharmacokinetics [21]. 2013 Jul-Aug;47(7-8):1039-44. doi: 10.1345/aph.1S176. Curr Opin Nephrol Hypertens. Rounding in the Calculator; Carboplatin Dosing Tips; ASCO on Dosing Chemo in Obesity: Equations and Conversions; Leucovorin Nomogram; Amputee Calculator Info; Vial Sizes and Concentrations Conceptualization, H.N.B., A.B. Geurtsen M.L., Kors W.A., Moll A.C., Smits C. Long-term audiologic follow-up of carboplatin-treated children with retinoblastoma. -, Clin Physiol. National Kidney Disease Education Program. Comparison of ethanol plasma-protein precipitation with plasma ultrafiltration and trichloroacetic acid protein precipitation for the measurement of unbound platinum concentrations. Ann Pharmacother. 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]. the clearance is typically calculated using the cockcroft and gault (C-G) formula. For all methods, the plot is skewed towards positive %PE indicating a trend towards overdosing of carboplatin. Her measured serum creatinine is 1.2 mg/dl. The https:// ensures that you are connecting to the Repeated measurements were considered as independent, therefore continuous measures of performance were tested using a Wilcoxon signed rank test. In conclusion, cystatin C-based eGFR equations for carboplatin dosing in children lead to more accurate carboplatin exposure. Common estimation equations for creatinine clearance or gfr. Prediction of total body water in infants and children. Use the Cockcroft and Gault method to calculate estimated creatinine clearance: Results: Serum creatinine cut-off values ranged from 0.36 mg/dL to 1 mg/dL. Ekhart C, Rodenhuis S, Schellens JH, Beijnen JH, Huitema AD. Filler G., Huang S.-H.S., Yasin A. 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. Although generally not labelled for pediatric patients, carboplatin is frequently used in children, mostly in the treatment of solid tumors. 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. This site needs JavaScript to work properly. There is no version of the Cockcroft Gault equation for use with standardized creatinine results. Studies evaluating carboplatin dos- ing are also being encouraged to address the current issues faced with dosing this drug. 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 ]. What is creatinine clearance? This indicates that an individual dosing strategy is warranted to obtain the optimal AUC. Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer. Cancer Chemother Pharmacol. 3. 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. Glomerular filtration rate in children with solid tumors: Normative values and a new method for estimation. Of all of the patients, 46.2% were female. Consequently, some patients undergo a higher systemic exposure, expressed as the area under the plasma concentration/time curve (AUC), than others when dosages of carboplatin are given on the basis of the body surface area. Dodgshun A.J., Quinlan C., Sullivan M.J. Cystatin C based equation accurately estimates glomerular filtration rate in children with solid and central nervous system tumours: Enough evidence to change practice? IBW is used based on the rationale that creatinine comes from lean muscle, so IBW would give a closer estimation of creatinine clearance. This is a breakdown product of creatine, an important component found in muscles that is cleared through the kidneys so its clearance is an important indicator of the kidneys' filtering function. Please enable it to take advantage of the complete set of features! Estimating glomerular filtration rate (GFR) in children. National Kidney Foundation. This approach assumes that the extra-renal clearance of carboplatin is linearly related to weight. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. The ePub format is best viewed in the iBooks reader. Veal G.J., Errington J., Tilby M.J., Pearson A.D.J., Foot A.B.M., McDowell H., Ellershaw C., Pizer B., Nowell G.M., Pearson D.G., et al. The importance of controlling carboplatin exposure is illustrated by the relationship between the carboplatin area under the concentration-time curve (AUC; equals dose divided by drug clearance), toxicity [11,12], and clinical efficacy [13]. The equation is: carboplatin dose (mg) = AUC x [GFR + 25]. ; validation, L.M.B., A.B. Ando Y, Shimokata T, Yasuda Y, Hasegawa Y. Exp Ther Med. Carboplatin dosing using eGFR may therefore be a more practical alternative to calculate the appropriate carboplatin dose. MR The main challenge in accurate carboplatin dos- ing is determining how to estimate renal function. Of note, both the Brandt and Millisor equations were derived in pediatric oncology patients. Example: Calculate the creatinine clearance of a 22 years old man who weighs 64 if the serum creatinine is 140 mg/dL. http://www.kidney.org/profession- als/KLS/gfr_calculator.cfm. ; methodology, A.B., G.L.K., H.N.B., A.J.W. an overprediction of the creatinine clearance and, by applying a modied Calvert formula with creatinine clearance as GFR to calculate the dose, produced a higher than expected carboplatin area under the concentration- time curve [7, 8]. The predicted creatinine production rate in females is 85% of the calculated value because they have a smaller muscle mass per kilogram, and it is muscle mass that determines creatinine production. -, Cancer Chemother Pharmacol. Furthermore, accuracy of carboplatin exposure in the present study compares surprisingly well to published data comparing eGFR equations with gold standard GFR measurements as reported in pediatric oncology studies [15,49]. National Kidney Disease Education Program CKD and Drug Dosing: Information for Providers. Janowitz T, Williams EH, Marshall A, Ainsworth N, Thomas PB, Sammut SJ, Shepherd S, White J, Mark PB, Lynch AG, Jodrell DI, Tavar S, Earl H. J Clin Oncol. 2015 Feb;50(2):103-7. doi: 10.1310/hpj5002-103. You may switch to Article in classic view. Qualitative variables are displayed as numbers (%). Creatinine Clearance; Rates; Insulin; Incidentals. 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. Bethesda, MD 20894, Web Policies 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 . Special thanks to Doreen Grun and Anke Carstensen for analyzing the samples and Sandra Diepenhorst for her share in the sampling. ; supervision, A.B., G.J.P. Simultaneous determination of intact cisplatin and its metabolite monohydrated cisplatin in human plasma. Unable to load your collection due to an error, Unable to load your delegates due to an error. was 2.8 months of age [30] and 1 month in Millisors cohort [15]. Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient. 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. The aim was to compare doses of carboplatin calculated using the Calvert formula and Chatelut formula and also to compare doses calculated using Calve We are experimenting with display styles that make it easier to read articles in PMC. Bjrk J., Nyman U., Berg U., Delanaye P., Dubourg L., Goffin K., Grubb A., Hansson M., Littmann K., sling-Monemi K., et al. In total, 38 clearance studies were performed, of which 18 (47%) were performed in children under the age of two years. Because of these challenges, questions arise as to what should be done by agencies like the US Food and Drug Administration (FDA) or the National Cancer Institute, or by pharmaceutical companies to combat this significant public health issue.
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