APE: absolute percentage prediction error, %PE: percentage prediction error. Choice of equations was based on performance in validation studies using gold standard GFR measurements [33]. In the total group as well as the two subgroups, the Schwartzcys equation performed best both in terms of bias and accuracy. A decreased renal (kidney) function would It is most commonly used to treat lung and ovarian cancers, but has been used off-label in many other diseases. The creatinine clearance used to calculate the carboplatin dose will be from PHYS 75 at Emory University eCollection 2017. Carboplatin and Liposomal Doxorubicin for Ovarian Cancer. Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. 2001 May;47(5):373-9. doi: 10.1007/s002800000260. 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. FOIA Use the Cockcroft and Gault method to calculate estimated creatinine clearance: Still, this did not improve accuracy of carboplatin exposure in the present study because all equations had a positive bias. The use of the Calvert formula to calculate carboplatin doses allows clinicians to achieve the appropriate carboplatin area under the concentration (AUC) curve. 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 Although highly accurate, these methods are not widely available and often too invasive and time-consuming for routine measurement of GFR [15]. US Food and Drug Administration. 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 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]. sharing sensitive information, make sure youre on a federal 8600 Rockville Pike ), 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; [email protected], 6Amsterdam UMC, Vrije Universiteit Amsterdam, Clinical Pharmacology and Pharmacy, 1081 HV Amsterdam, The Netherlands; [email protected], 7Laboratory of Medical Oncology, Amsterdam University Medical Center, VUMC, 1081 HV Amsterdam, The Netherlands; [email protected] (R.J.H. While performing well in the overall analysis, anthropometric dosing is hampered by a weight-dependent change in bias. For this, the standard pharmacokinetic formula [dose = clearance carboplatin x target AUC] is used. Different studies employ different formulas or approaches to carboplatin dosing. Simultaneous determination of intact cisplatin and its metabolite monohydrated cisplatin in human plasma. Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients. Details of these equations can be found in Table 1. Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin is a chemotherapeutic agent that is usually dosed based on body surface area or weight. 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]. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. . Ryan Pritchard E, Waddell JA, Solimando DA Jr. Hosp Pharm. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Estimating glomerular filtration rate (GFR) in children. Dose modification . National Kidney Foundation K/DOQI Clinical Practice Guidelines for chronic kidney disease: Evaluation, classification and stratification. 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. 2017 Oct 5;8:76. doi: 10.4103/ijpvm.IJPVM_40_17. 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 . This is more marked for the creatinine-based than the cystatin C-based eGFR equations and anthropometric dosing. A high AUC correlates with increased toxicity, thus increasing the risks of the treatment, but in the case of a low AUC the therapeutical efficacy decreases. The United Kingdom Childrens Cancer Study Group. This can result in suboptimal treatment [40] since underestimation of creatinine will lead to an overestimation of GFR and overdosing of carboplatin with the potential of increased toxicity. The emerging standard for calculation of carboplatin therapy dosage is to base the dose on creatinine clearance as a surrogate for carboplatin clearance. ; funding acquisition, H.N.B. Currently, there is not much evidence for its utility in the context of car- boplatin dosing. Clipboard, Search History, and several other advanced features are temporarily unavailable. Wells J.C.K., Fewtrell M.S., Davies P.S.W., Williams J.E., Coward W.A., Cole T.J. J Clin Oncol. Although the Calvert formula is the standard method to calculate the dose of carboplatin, there is no consensus how to determine the glomerular filtration rate (GFR) without using [51Cr]-ethylenediamine tetraacetic acid (51Cr-EDTA). Donahue A, McCune JS, Faucette S, Gillenwater HH, Kowalski RJ, Socinski MA, Lindley C. Cancer Chemother Pharmacol. Carboplatin dosing using eGFR may therefore be a more practical alternative to calculate the appropriate carboplatin dose. Prediction of total body water in infants and children. Carboplatin Dosing Accuracy by Estimation of Glomerular Filtration versus Creatinuria in Cancer Patients. MeSH Qaddoumi I., Bass J., Wu J., Billups C.A., Wozniak A.W., Merchant T.E., Haik B.G., Wilson M.W., Rodriguez-Galindo C. Carboplatin-associated ototoxicity in children with retinoblastoma. Marina N.M., Rodman J.H., Murry D.J., Shema S.J., Bowmans L.C., Jones D.P., Furman W., Meyer W.H., Pratt C.B. First of all the creatinine clearance is calculated using the modified modified Cockcroft-Gault formula which is given below: Leon O. Jacobson Professor of Medicine Director, Center for Personalized Therapeutics Associate Director for Clinical Sciences Cancer Research Center The formulae used in this study are listed below. 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. Each symbol indicates the same patients in all figures. Verschraagen M., Boven E., Ruijter R., Born K., Berkhof J., Hausheer F.H., Vijgh W.J.F. In overweight and obese patients they were superior in reducing mean overdose from 24% to roughly 15% (predicted normal weight, CKD-EPI) and 10% (adjusted body weight) and from 25% to 9%, 8% and 4%, respectively. ; supervision, A.B., G.J.P. [50] found no advantage of eGFR-based dosing in patients with a GFR above 50 mL/min. Hjorth L., Wiebe T., Karpman D. Correct evaluation of renal glomerular filtration rate requires clearance assays. Acoustic feedback enables safe and reliable carboplatin delivery across the blood-brain barrier with a clinical focused ultrasound system and improves survival in a rat glioma model. 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. Epub 2013 Jun 11. Furthermore, since there was a dosing difference in children below and above 10 kg, these were also analyzed separately. Mosteller R.D. The aim was to compare doses of carboplatin calculated using the Calvert formula and Chatelut formula and also to compare doses calculated using Calve 1989;7:1748-1756. H&O Can you provide some background on carboplatin? Unable to load your collection due to an error, Unable to load your delegates due to an error. Would you like email updates of new search results? The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)]. MR When deciding what factors to incorporate into the calculation of carboplatin dosing, one generally utilizes existing clinical trial data that targeted a speci fic area under the concentration-time curve (AUC). When to Use Pearls/Pitfalls Why Use Sex Female Male Age years Weight lbs Creatinine mg/dL and transmitted securely. Solved Example: For piperacillin (an antibiotic) standard dosing for patients is: What dose should be given to the above patient? 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%. 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. ), 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; [email protected] (E.d.B. In total, 13 children were included. and Creatinine clearance (CrCl) values range from 1.24-2.24 mL/second. The cystatin C-based equations performed slightly better than the creatinine-based equations, in particular in younger children. Historically, this error was balanced by an error of almost equal magnitude in the measurement of the serum creatinine. The .gov means its official. Hosp Pharm. Creatinine Clearance; Rates; Insulin; Incidentals. Binary performance outcome of the different eGFR equations were compared using the McNemar test, Chi-squared test or Fishers exact test. ; 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. 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. Soveri I., Berg U.B., Bjrk J., Elinder C.-G., Grubb A., Mejare I., Sterner G., Bck S.-E. For patients with abnormal renal function, the usual formulas are less likely to be problematic. We acknowledge a number of limitations in our study. 1Emma Childrens Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, 1081 HV Amsterdam, The Netherlands; [email protected] (H.N.B. http://www.nkdep.nih.gov/professionals/gfr_calculators/idms_con.htm. Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae. 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? Okamoto H, Nagatomo A, Kunitoh H, Kunikane H, Watanabe K. Cancer Chemother Pharmacol. In children, muscle mass increases with age so that serum creatinine can only be used to monitor renal function after correction for anthropometric data or age [39]. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, carboplatin, children, renal function-based dosing, glomerular filtration rate, cystatin C, retinoblastoma. Would you like email updates of new search results? Still, none of the patients here showed hyperfiltration as all eGFR measurements were below 140 mL/min/1.73 m2. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as calculated by formulae using serum creatinine (SCR; Cockcroft-Gault, Jelliffe, and Wright) is . 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 ]. Creatinine Clearance (Cockcroft-Gault Equation) - MDCalc Creatinine Clearance (Cockcroft-Gault Equation) Calculates CrCl according to the Cockcroft-Gault equation. [30] and Millisor et al. Accessibility 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. Please note that dose is provided in mg not mg/m 2. The dotted lines indicate the thresholds of percentage error of +25% and 10%. and E.d.B. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. Based on our data this approach seems appropriate as we observed no systematic relation between %PE and bodyweight in the Newell equation with any of the eGFR methods used. 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]. This has been studied extensively in adults [ 18 , 19 ]. Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae. Samples were obtained at 2.5, 8, 10, and 23 h after the start of infusion. the kidneys are working and then calculate the dose based on the kidney function. Unable to load your collection due to an error, Unable to load your delegates due to an error. Serum creatinine cut-off values ranged from 0.36 mg/dL to 1 mg/dL. result in decreased creatinine clearance. This was adjusted for children by introducing a weight-dependent term of 0.36 (i.e., 25 divided by the weight of an average adult of 70 kg) to be added to GFR in the Newell equation [6]. Carboplatin clearance (ml/min) = GFR + 25. 1998;42(4):307-12. doi: 10.1007/s002800050822. 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). Discrepancies between the Cockcroft-Gault and Chronic Kidney Disease Epidemiology (CKD-EPI) Equations: Implications for Refining Drug Dosage Adjustment Strategies. The weight used in the above equations is IBW. Implications of the CKD-EPI GFR estimation equation in clinical practice. ; investigation, H.N.B., A.J.W., R.J.H., B.S.-W. and F.C.H.A. Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in oncology patients. 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]. All dosing methods resulted in a positive bias with median %PE values ranging from 4.1 to 21%. Therefore, it is assumed there is limited additional value of adding urea in an equation for this specific population. 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. The equation is: carboplatin dose (mg) = AUC [GFR + 25]. Leion F., Hegbrant J., den Bakker E., Jonsson M., Abrahamson M., Nyman U., Bjrk J., Lindstrm V., Larsson A., Bkenkamp A., et al. The ePub format is best viewed in the iBooks reader. and G.J.P. Renal function was assessed before each course of carboplatin. This model was implemented in MWPharm++ 1.35 (Mediware a.s., Praha, Czech Republic). Patient-specific data were collected and used to calculate a carboplatin dose before and after the SCr assay change using the Cockcroft-Gault equation, with the Calvert et al. 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. Fluid electrolyte changes in physically healthy subjects during prolonged re-striction of motor activity and daily hyperhydration. 2. Licensee MDPI, Basel, Switzerland. the display of certain parts of an article in other eReaders. MR Carboplatin is a platinum chemotherapy drug that is administered as an intravenous infusion. ; formal analysis, M.E.v.d.V. Carboplatin dosing. Mirjam E. van de Velde, Emil den Bakker, [], and Arend Bkenkamp. The necessity of adjusting the serum PAP-Cr in carboplatin dosing formulas was confirmed as the bias and precision of the estimation was seen in all of the participating institutions as shown by decrease in the absolute value of MPE and RMSE for each institution. Cancer Chemother Pharmacol. GFR calculator. and 19.3% capped both creatinine clearance and serum creatinine. In line with the eGFR data, observed carboplatin clearance differed between both age groups even when normalized for BSA (84.5 mL/min/1.73 m2 in the younger versus 116.7 mL/min/1.73 m2 in the older patients). Studies evaluating carboplatin dos- ing are also being encouraged to address the current issues faced with dosing this drug. The equation is: carboplatin dose (mg) = AUC x [GFR + 25]. Veal G.J., Errington J., Hayden J., Hobin D., Murphy D., Dommett R.M., Tweddle D.A., Jenkinson H., Picton S. Carboplatin therapeutic monitoring in preterm and full-term neonates.