Lung Cancer 79 (2013) Contents lists available at SciVerse ScienceDirect. Lung Cancer. jou rn al h om epa ge:

Transcription

1 Lung Cancer 79 (2013) Contents lists available at SciVerse ScienceDirect Lung Cancer jou rn al h om epa ge: Carboplatin dose calculation in lung cancer patients with low serum creatinine concentrations using CKD-EPI and Cockcroft Gault with different weight descriptors Dieter Kaag Pharmacy Department, Thoraxklinik Heidelberg, University of Heidelberg, Amalienstrasse 5, Heidelberg, Germany a r t i c l e i n f o Article history: Received 18 September 2012 Received in revised form 11 October 2012 Accepted 16 October 2012 Keywords: Cytotoxic agent Carboplatin Cockcroft Gault CKD-EPI Glomerular filtration rate Creatinine clearance Serum creatinine Adjusted body weight Predicted normal weight a b s t r a c t Study objectives: Carboplatin dosing using the Calvert and Cockcroft Gault formulae in patients with low serum creatinine levels is discussed controversially. We conducted a retrospective analysis applying the CKD-EPI formula and the alternate size descriptors adjusted body weight and predicted normal weight in the Cockcroft Gault equation for calculating the carboplatin dose. Methods: Data were collected retrospectively from 128 lung cancer patients with serum creatinine <0.8 mg/dl (71 mol/l) who had received chemotherapy that was mostly platinum-based. Serum creatinine concentration for renal function estimation and measured creatinine clearance (24-h urine collection) were available on the same day from these patients. Actual doses were calculated based on the Cockcroft Gault formula with total body weight. For the study purpose doses were recalculated using Cockcroft Gault with adjusted body weight and predicted normal weight and CKD-EPI. Subgroup analyses were performed for gender and body mass index. Results: All alternate dose calculations were not inferior to the calculation based on Cockcroft Gault using total body weight. 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. Best performed the combination of Cockcroft Gault with adjusted body weight. Conclusion: 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 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Lung cancer is the most common neoplasm worldwide, responsible for 13% (1.6 million) of the total cases and 18% (1.4 million) of the deaths in 2008 [1]. Overall survival rates are poor, with data from 2000 to 2002 indicating 1- and 5-year relative survival expectations for about 37% and 12% of patients, respectively [2]. Along with surgery and radiotherapy, chemotherapy represents an important treatment option for lung cancer. Combination chemotherapy, mostly platinum-based, prolongs survival in patients with small-cell lung cancer (SCLC) as well as advanced non-small-cell lung cancer (NSCLC) [3,4]. Tailoring doses of cytotoxic drugs to individual cancer patients is common practice today; however, there are unsolved questions regarding dosing with such drugs. For example the dosing of many Corresponding author. Tel.: ; fax: addresses: dieter.kaag@thoraxklinik-heidelberg.de, dkaag@gmx.de cytotoxics according to the patient s body surface area (BSA) is frequently questioned [5]. For the renally excreted carboplatin a very close relationship between its dose, area under the concentration time curve (AUC), toxicity and therapeutic effect could be demonstrated allowing the development of an individualised dosing based on renal function and the Calvert formula [6 8]. Since the original chromium-51 ethylene diamine tetra-acetate ([ 51 Cr]EDTA) method used by Calvert is too costly and time-consuming for routine measurement of glomerular filtration rate (GFR) most clinicians use the Cockcroft Gault (CG) formula for estimating creatinine clearance (CrCl) as surrogate for renal function [9]. With introduction of CG and other formulae discussion started about systematic dosing inaccuracies caused by suboptimal estimation of renal function compared with the [ 51 Cr]EDTA method [3]. For example Poole, Dooley et al. examined different formulae for GFR calculation in 122 cancer patients and found that the CG formula using total body weight (TBW) overestimated renal function in patients with GFR < 50 ml/min and underestimated renal clearance in patients with GFR > 100 ml/min in both sexes /$ see front matter 2012 Elsevier Ireland Ltd. All rights reserved.

2 D. Kaag / Lung Cancer 79 (2013) [10,11] compared to the technetium-99m diethylene triamine penta-acetate ([ 99m Tc]DTPA) method for clearance measurement which is comparable to [ 51 Cr]EDTA method as a gold standard. There has also been considerable focus on the use of CrCl as marker for GFR. Renal clearance of creatinine is not only due to glomerular filtration but also to tubular secretion and therefore leads to an overestimation of GFR between 12 and 24%. If the colorimetric alkaline pikrate method (Jaffe method) is used for creatinine detection this possibly results in an overestimation of serum creatinine (SCr) of 20 30% due to interfering substances ( noncreatinine chromogens ) in serum samples but not in urine; this method can therefore result in an underestimating of GFR. By coincidence, this error approximately compensates the difference between true CrCl and GFR. Hence a correction of the calculated carboplatin dose may not be necessary in this setting [12]. If an enzymatic assay is used for SCr measurement this can result in an overestimation of GFR and the resulting carboplatin dose. Léger et al. demonstrated that using the Chatelut formula to estimate carboplatin clearance resulted in a difference of 13.9% between an enzymatic SCr assay and the kinetic method [13]. A difference of about 10% between these two methods was also found by Levey et al. regarding the Modification of Diet in Renal Disease (MDRD) equation [14]. Furthermore, the introduction of more accurate SCr assays traceable to isotope dilution mass spectrometry (IDMS) as gold standard resulted in lower measured SCr concentrations and hence higher calculated carboplatin doses compared to a non-idms-traceable enzymatic assay [15]. These possible systematic errors also affect the Cockcroft Gault formula but are not routinely considered for renal clearance calculation in clinical practice. With regard to overweight and obese patients in particular, much attention has been paid to the kind of weight descriptor used for dose calculation. Encouraging results were obtained using adjusted body weight (ABW) [16] or predicted normal weight (PNWT) [17] in the CG equation instead of TBW. Both weight descriptors were studied in cancer patients receiving carboplatin, resulting in more accurate dosing than using TBW [18 22]. The 2009 introduced Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [23] has not yet been widely tested for carboplatin dosing but nevertheless gave encouraging results compared to dose calculation according to CG with TBW (CG-TBW) and deserves further examination [21,24,25]. The possible inaccuracies of calculating renal clearance in cancer patients with low SCr concentrations are another subject for ongoing debate. Rounding low SCr concentrations to either 0.68 mg/dl (60 mol/l) or 0.8 mg/dl (71 mol/l) in renal function estimation and subsequent carboplatin dose calculation gave conflicting results and cannot be recommended in general until further prospective studies are available [19,26,27]. A further area of uncertainty by calculating instead of measuring renal function for drug dosing represents the growing number of very old patients, possibly cachectic and with insufficient renal function. Only few octogenarians were included in the development of the CG formula (7% of participants) [9], none or nearly none in the MDRD [28] and CKD-EPI formulae (0% and <0.1%, respectively) [23]. Some studies indicate that in this patient population MDRD and CKD-EPI formulae have the potential to overestimate renal function. Therefore, a new formula especially to assess kidney function in persons 70 years or older has been proposed recently [29]. A new attempt to overcome the limitations of existing methods for estimating CrCl that rely only on the serum marker creatinine (together with demographical and morphologic factors) like the CG formula, uses cystatin C (cysc) as an additional biological covariate. cysc is a small protein that is endogenously produced in most nucleated cells at a constant rate and not renally secreted but exclusively filtrated. Therefore it is supposed to meet the criteria for an ideal GFR marker. Regarding dose calculation of carboplatin, a new formula containing cysc and creatinine as serum markers led to encouraging results in different patient populations including patients with low SCr values. However, cysc determination is not available in many clinical laboratories at present [30,31]. The aim of this study was to focus on possible dosing inaccuracies in adult lung cancer patients with serum creatinine values of less than 0.8 mg/dl (71 mol/l). It reevaluated previously published work which focused on rounding these low SCr levels to 0.8 mg/dl or 0.68 mg/dl to improve carboplatin dosing [27]. Because replacing TBW in the CG equation by alternate weight descriptors ABW or PNWT, or applying the CKD-EPI equation for GFR estimation showed promising results regarding carboplatin AUC dose calculation in obese patients with a wide range of SCr concentrations [21], these calculation methods were studied retrospectively in the existing data set of patients with low SCr concentrations. 2. Methods Data from 128 adult lung cancer patients were obtained retrospectively from local records, especially the pharmacy department (for patient data, see Table 1). Criteria for inclusion were: patients presented with SCr < 0.8 mg/dl; patents were receiving chemotherapy, mostly platinum-based, in the years ; values for SCr and CrCl calculated from 24-h urine collection were available on the same day. Most patients received carboplatin with a target AUC of 5 calculated according to the Calvert and Cockcroft Gault formulae using actual SCr values and TBW. For the remaining patients receiving another chemotherapeutic regimen instead of carboplatin, dose was calculated as if these patients had received carboplatin. These resulting doses were compared with the corresponding recalculated doses using the Calvert formula with CrCl derived from 24-h urine collection (mcrcl), Calvert and CG formulae replacing TBW by ABW or PNWT, or Calvert with CKD-EPI equation adjusted for BSA (CKD-EPI-BSA). Calculations were done for the whole patient population and different subgroups (gender, BMI < 18.5, 18.5 BMI < 25, Table 1 Patient characteristics. Mean all (range), n = 128 Mean males (range), n = 56 Mean females (range), n = 72 Age [years] 59 (35 80) 60 (40 80) 58 (35 78) Height [cm] 168 ( ) 174 ( ) 164 ( ) Weight [kg] 69.4 ( ) 76.7 ( ) 63.7 ( ) BMI [kg/m 2 ] 24.4 ( ) 25.2 ( ) 23.8 ( ) BSA (Mosteller) [m 2 ] 1.79 ( ) 1.92 ( ) 1.69 ( ) Serum creatinine [mg/dl] 0.67 ( ) 0.69 ( ) 0.65 ( ) Creatinine clearance (24h urine collection) [ml/min] 113 (21 269) 136 (55 269) 96 (21 171) BMI: body mass index; BSA: body surface area.

3 56 D. Kaag / Lung Cancer 79 (2013) BMI < 30, BMI 30, according to WHO classification for underweight, normalweight, overweight and obese, respectively [32]), using bias and precision. Bias was assessed as mean percentage error (MPE), calculated as the percentage difference between estimated CrCl (ecrcl) and mcrcl (in relation to CG, since this formula was calibrated to CrCl) or between estimated GFR (egfr) and mcrcl (since CKD-EPI was calibrated to GFR). A positive bias indicates overestimation of CrCl and a negative bias indicates underestimation. Precision was calculated as mean absolute percentage error (MAPE). The larger the MAPE, the less precise the calculation results in predicting actual CrCl and hence GFR. MPE [%] = 1/n (D D mcrcl ) 100/D mcrcl MAPE [%] = 1/n D D mcrcl 100/D mcrcl D refers to carboplatin dose calculated either with CG-TBW, CG- ABW, CG-PNWT, or CKD-EPI-BSA. D mcrcl refers to carboplatin dose calculated with mcrcl, n represents patient number. For the CrCl reference method mcrcl the nursing staff instructed patients to collect their urine for 24 h beginning at morning and to drink sufficiently during this time. If the collected urine volume was implausibly low, patients were fasting most of that day, or were supposed to excrete radioisotopes, the respective samples were discarded. From the resulting urine volume per 24 h V 24 and the creatinine concentrations in urine UCr and serum SCr, mcrcl was calculated as follows: mcrcl [ml/min] = V 24 [ml] UCr [mg/dl] 1440/SCr [mg/dl] ; 1440 : converting factor from 24 h to 1 min. Serum creatinine was measured using a kinetic Jaffé method (HiCo Creatinine Jaffé method, rate-blanked, with compensation, traceable to isotope dilution mass spectrometry (IDMS), Roche Diagnostics) until June 2006 and an enzymatic method thereafter (Konelab TM /T Series Creatinine (Enzymatic), IDMS traceable, Thermo Fisher Scientific). The non-parametric Wilcoxon matched-pairs test with a level of significance of p = 0.05 was used to compare results from mcrcl and ecrcl/egfr, respectively. Calculations were done with Microsoft Excel Office XP and SPSS, version Calculation methods: Calvert formula [6]: dose = target AUC [mg/ml min] (GFR [ml/min] + 25) Cockcroft Gault (CG) [9]: ecrcl [ml/min] = (140 age) Wt [kg] 0.85 (if female)/(72 SCr [mg/dl])wt: body weight Adjusted body weight (ABW) [16]: ABW = IBW (TBW- IBW). IBW means ideal body weight according to Devine and is calculated as follows: Male: IBW [kg] = 49.9 kg kg/cm (height cm) Female: IBW [kg] = 45.4 kg kg/cm (height cm) Predicted normal weight (PNWT) [17]: Male: PNWT [kg] = 1.57 TBW BMI TBW 10.5 Female: PNWT [kg] = 1.75 TBW BMI TBW 12.6 CKD-EPI [23]: Males with SCr 0.9: egfr/1.73 m 2 = 141 (SCr/0.9) Males with SCr > 0.9: egfr/1.73 m 2 = 141 (SCr/0.9) Females with SCr 0.7: egfr/1.73 m 2 = 144 (SCr/0.7) Females with SCr > 0.7: egfr/1.73 m 2 = 144 (SCr/0.7) Table 2 Carboplatin AUC 5 doses resulting from measured (24 h urine collection) CrCl, estimated CrCl (according to Cockcroft Gault using total body weight, adjusted body weight and predicted normal weight), estimated glomerular filtration rate using CKD-EPI and significance p (Wilcoxon) for patients with SCr < 0.8 mg/dl. p p Mean dose ± SD according to Calvert/CKD-EPI-BSA [mg] p Mean dose ± SD according to Calvert/CG-PNWT [mg] p Mean dose ± SD according to Calvert/CG-ABW [mg] Mean dose ± SD according to Calvert/CG-TBW [mg] Mean dose ± SD according to Calvert/mCrCl [mg] All, n = ± ± ± 134 < ± ± Males, n = ± ± ± 110 < ± 116 < ± 65 <0.01 Females, n = ± ± ± ± ± BMI < 18.5 kg/m 2, n = ± ± ± ± ± BMI < 25 kg/m 2, n = ± ± 117 < ± 117 < ± 116 < ± 70 < BMI < 30 kg/m 2, n = ± ± ± ± ± BMI 30 kg/m 2, n = ± ± ± ± ± AUC: area under the concentration time curve; CrCl: creatinine clearance; SCr: serum creatinine; CG: Cockcroft Gault; BMI: body mass index; SD: standard deviation; TBW: total body weight; ABW: adjusted body weight; PNWT: predicted normal weight; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration.

4 D. Kaag / Lung Cancer 79 (2013) Table 3 Bias (as mean percentage error) and precision (as mean absolute percentage error) of calculated Carboplatin AUC 5 doses in relation to the dose resulting from measured CrCl. Calculations used Cockcroft Gault with total body weight, adjusted body weight and predicted normal weight for estimating CrCl and CKD-EPI for estimating GFR in patients with SCr < 0.8 mg/dl. Calvert/CG-TBW Calvert/CG-ABW Calvert/CG-PNWT Calvert/CKD-EPI-BSA All, n = 128 4/25 2/22 0/23 0/22 Males, n = 56 1/23 6/20 5/21 7/22 Females, n = 72 8/27 1/24 4/25 6/23 BMI < 18.5 kg/m 2, n = 8 11/22 1/22 7/23 8/ BMI < 25 kg/m 2, n = 73 8/20 9/19 7/19 6/18 25 BMI < 30 kg/m 2, n = 32 24/36 10/29 16/31 15/29 BMI 30 kg/m 2, n = 15 25/33 4/25 9/26 8/25 AUC: area under the concentration time curve; CrCl: creatinine clearance; SCr: serum creatinine; GFR: glomerular filtration rate; CG: Cockcroft Gault; BMI: body mass index; SD: standard deviation; TBW: total body weight; ABW: adjusted body weight; PNWT: predicted normal weight; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration. Factor for African-Americans: For adjusting to actual patient BSA, the factor BSA/1.73 m 2 had to be added resulting in CKD-EPI-BSA. 3. Results The present study included 128 adult lung cancer patients treated at the Thoraxklinik Heidelberg, 56% female and aged between 35 and 80 years, with SCr levels between 0.38 and 0.79 mg/dl, and mcrcl ml/min (see Table 1). Regarding the entire patient population, using CG-TBW for ecrcl and furthermore carboplatin dose calculation resulted in virtually the same dose as using the standard method mcrcl (Calvert/CG- TBW: 670 mg, Calvert/mCrCl: 691 mg). Replacing TBW by ABW or PNWT or applying CKD-EPI-BSA gave significantly lower results, though bias of all methods was below 5%. The overall lower results for dose calculations based on ecrcl and egfr compared to dosing according to mcrcl were due to significantly lower results in the male subgroup whereas results were not significantly different in the female subgroup. Nevertheless mean percentage errors (bias) in these two subgroups were below 10% for all ecrcl and the egfr methods. Focusing on BMI subgroups revealed a trend to overestimate renal function with increasing BMI using CG-TBW as calculation method. Obese patients with BMI 30 received a mean 25% overdose compared to the dose resulting from mcrcl (835 mg vs. 716 mg). This trend was not seen to that extent applying the other methods. Biases of all remaining methods were below 10% in this subcategory and maximally 16% in overweight patients (CG-TBW: 24%). Best performance in all BMI subgroups showed dose calculation according to CG-ABW with biases below or equal to 10% resulting in carboplatin doses not significantly different to the standard dose using mcrcl except for the subgroup of normal weight patients. Precision was roughly the same for all dose calculation methods with a tendency to increase with higher BMI, especially for ecrcl according to CG-TBW (for all results see Tables 2 and 3). 4. Discussion For 128 adult lung cancer patients with serum creatinine concentrations below 0.8 mg/dl (71 mol/l) treated at our institution, application of the weight descriptors ABW or PNWT instead of TBW in the CG equation or using the new CKD-EPI formula for carboplatin AUC dose calculation would have improved dosing accuracy especially in overweight and obese patients with no loss of accuracy in underweight and normalweight patients. It is well known that using CG-TBW for CrCl calculation may overestimate renal function in obese patients with a wide range of SCr levels [33]. In the present study, all calculation methods, especially CG-TBW, showed a tendency to overestimate carboplatin dose in overweight and obese patients compared to the dosing algorithm based on mcrcl. However, these trends were not significant for all included methods. Of note is that in the present study the weight descriptors ABW and PNWT were used over the entire range of BMI and not only for overweight and obese subjects with the consequence of maintaining or improving dosing accuracy also for underweight and normalweight patients (see Table 3). The present investigation builds on previously published work in the same patient population finding that rounding low SCr concentrations to 0.8 mg/dl worsened bias in 81 patients with BMI between 13.6 and 25 and improved bias in 47 overweight and obese patients compared to calculation with actual SCr values [27]. That study was done to prove the concept of Herrington et al. who found that rounding SCr levels lower than 0.8 mg/dl in 9 cancer patients with BMI between 18.6 and 25.3, who received carboplatin-containing chemotherapy, improved dosing accuracy [19]. Our findings were in contrast to theirs concerning the respective BMI cohort, motivating us to search for different solutions to improve dosing in our patients. Alternate size descriptors such as ABW and PNWT in the CG formula and application of the CKD- EPI equation to calculate carboplatin doses showed promising results in several investigations in oncology patients not selected according to their SCr concentrations [18 22,24] which is discussed elsewhere [21]. Another support using CKD-EPI for carboplatin dosing in lung cancer patients came from a recent study. Unfortunately the authors did neither correct for actual BSA which could have improved CKD-EPI-based dosing further nor did they report subgroup results despite an impressive sample size of 218 patients [25]. In the present study dose calculation using CKD-EPI-BSA performed better than CG-TBW but was inferior to CG-ABW especially in overweight patients. Assumptions on the clinical significance of the results can be based on the generally accepted finding that the therapeutic window of carboplatin comprises AUC 5 7 [8]. Dosing regimens that lead to AUC 4 or below (or in other words a bias of 20% related to a target AUC 5) can therefore be regarded as subtherapeutic. All calculation methods in the present study led to a bias of less than 20% with the exception of CG-TBW in patients with BMI 25. Therefore the clinical implications selecting any of the studied dosing methods may have been moderate for most of our patients. To our knowledge this is the first study investigating ABW, PNWT and CKD-EPI for dose calculation in such a group of patients with low SCr values. The strength of our study consisted of a large patient population enabling us to study gender and BMI subgroups. Limitations of our study mainly result from the retrospective character and the possible uncertainties of measuring CrCl via 24-h urine collection which is prone to error and no longer recommended routinely to estimate kidney function [34] but which is, nevertheless, the only available reference method for clinics with

5 58 D. Kaag / Lung Cancer 79 (2013) limited resources. The fact that our patients did not necessarily receive carboplatin but cisplatin or other chemotherapeutic regimens did not alter our calculations of renal function and hence our results. The use of two serum creatinine assays in the study period did not affect our results substantially because all measurements for a certain patient were done with the same method. Possible CrCl values of higher percentage and hence carboplatin dosages resulting from lower SCr values assayed with the enzymatic method compared with the Jaffé method did not affect calculation of MPE (bias) and MAPE (precision). In conclusion, carboplatin dose calculation based on adjusted body weight used in the Cockcroft Gault equation improved accuracy especially in overweight and obese lung cancer patients. Desirable future studies should be sufficiently powered and use a more reliable reference method for determining GFR than 24-h urine collection. Only then can more definite conclusions be drawn and changes in clinical practice justified. Conflict of interest None declared. Acknowledgements The author would like to thank Thomas Muley for his biostatistical support, and Wilma Strothenke, Stephan Liersch and Eva Fornefeld for their valuable advice on the preparation of the manuscript. References [1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61: [2] Brenner H, Francisi S, de Angelis R, Marcos-Gragera R, Verdecchia A, Gatta G, et al. Long-term survival expectations of cancer patients in Europe Eur J Cancer 2009;45: [3] Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG, et al. Non-smallcell lung cancer. Lancet 2011;378: [4] Van Meerbeeck JP, Fennell DA, De Ruysscher DKM. Small-cell lung cancer. Lancet 2011;378: [5] Mathijssen RHJ, de Jong FA, Loos WJ, van der Bool JM, Verweij J, Sparreboom A. Flat-fixed dosing versus body surface area-based dosing of anticancer drugs in adults: does it make a difference? Oncologist 2007;12: [6] Calvert AH, Newell DR, Gumbrell LA, O Reilly S, Burnell M, Boxall FE, et al. Carboplatin dosage, prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989;7: [7] Calvert AH, Egorin MJ. Carboplatin dosing formulae: gender bias and the use of creatinine-based methodologies. Eur J Cancer 2002;38:11 6. [8] Alberts DS, Dorr RT. New perspectives on an old friend: optimizing carboplatin for the treatment of solid tumors. Oncologist 1998;3: [9] Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16: [10] Poole SG, Dooley MJ, Rischin D. A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc 99m DTPA clearance) in cancer patients. Ann Oncol 2002;13: [11] Dooley MJ, Poole SG, Rischin D, Webster LK. Carboplatin dosing: gender bias and inaccurate estimates of glomerular filtration rates. Eur J Cancer 2002;38: [12] Coresh J, Astor BC, McQuillan G, Kusek J, Greene T, Van Lente F, et al. Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 2002;39: [13] Léger F, Séronie-Vivien S, Makdessi J, Lochon I, Delord JP, Sarda C, et al. Impact of the biochemical assay for serum creatinine measurement on the individual carboplatin dosing: a prospective study. Eur J Cancer 2002;38:52 6. [14] Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, et al. Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007;53: [15] Murray B, Bates J, Buie L. Impact of a new assay for measuring serum creatinine levels on carboplatin dosing. Am J Health-Syst Pharm 2012;69: [16] Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004;58: [17] Duffull SB, Dooley MJ, Green B, Poole SG, Kirkpatrick CMJ. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet 2004;43: [18] Ekhart C, Rodenhuis S, Schellens JHM, Beijnen JH, Huitema ADR. Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter? Cancer Chemother Pharmacol 2009;64: [19] Herrington JD, Tran HT, Riggs MW. Prospective evaluation of carboplatin AUC dosing in patients with a BMI 27 or cachexia. Cancer Chemother Pharmacol 2006;57: [20] Sparreboom A, Wolff AC, Mathijssen RHJ, Chatelut E, Rowinsky EK, Verweij J, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 2007;25: [21] Kaag D. Retrospective evaluation of various weight descriptors and formulae for dose calculation of carboplatin in obese patients. Krankenhauspharmazie 2012;33:2 10 [in German]. [22] Boumedien F, Arsenault Y, LeTarte N. Impact of weight and creatinine measurements in carboplatin dosing ASCO annual meeting proceedings. J Clin Oncol 2012;30(Suppl.):e13027 [abstract e13027]. [23] Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro III AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150: [24] Redal-Baigorri B, Stokholm KH, Rasmussen K, Jeppesen N. Estimation of kidney function in cancer patients. Dan Med Bull 2011;58:A4236. [25] Trobec K, Knez L, Brguljan PM, Cufer T, Lainscak M. Estimation of renal function in lung cancer patients. Lung Cancer 2012;76: [26] Dooley MJ, Singh S, Rischin D. Rounding of low serum creatinine levels and consequent impact on accuracy of bedside estimates of renal function in cancer patients. Br J Cancer 2004;90: [27] Kaag D, Steins M. Impact of rounding low serum creatinine concentrations on the accuracy of carboplatin AUC dosing. Eur J Hosp Pharm Sci 2011;17:13 7. [28] Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130: [29] Schaeffner ES, Ebert N, Delanaye P, Frei U, Gaedeke J, Jakob O, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med 2012;157: [30] Schmitt A, Gladieff L, Lansiaux A, Bobin-Dubigeon C, Etienne-Grimaldi MC, Boisdron-Celle M, et al. A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients. Clin Cancer Res 2009;15: [31] Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012;367:20 9. [32] BMI classification. 3.html [accessed ]. [33] Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function measured and estimated glomerular filtration rate. N Engl J Med 2006;354: [34] Traynor J, Mactier R, Geddes CC, Fox JG. How to measure renal function in clinical practice. BMJ 2006;333:733 7.