New model for estimating glomerular filtration rate in patients with cancer results improves accuracy of carboplatin chemotherapy dosing


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Edward Williams1,Tobias Janowiz1,Andrea Marshall2,Nicola Ainsworth3,Peter Thomas4,Stephen Sammut1,Scott Shepherd5,Jeff White5,Patrick Mark5,Andy Lynch1,Duncan Joderell1,Simon Tavaré1,Helena Earl6
1Cancer Research UK Cambridge Institute,2Warwick Medical School,3Queen Elizabeth Hospital, King's Lynn,4University of Cambridge,5Beatson West of Scotland Cancer Centre,6Department of Oncology, University of Cambridge

Abstract

Background

The glomerular filtration rate (GFR) is essential for carboplatin chemotherapy dosing; however, the best method to estimate GFR in patients with cancer is unknown. We identify the most accurate and least biased method.(1)

Method

We obtained data on age, sex, height, weight, serum creatinine concentrations, and results for GFR from chromium-51 (51Cr) EDTA excretion measurements (51Cr-EDTA GFR) from white adult patients with histologically confirmed cancer diagnoses at the Cambridge University Hospital NHS Trust, United Kingdom. We developed a new multivariable linear model for GFR using statistical regression analysis. 51Cr-EDTA GFR was compared with the estimated GFR (eGFR) from seven published models and our new model, using the statistics root-mean-squared-error (RMSE) and median residual and on an internal and external validation data set. We also performed a comparison of carboplatin chemotherapy dosing accuracy.

Results

Between August 2006 and January 2013, data from 2,471 patients were obtained. The new model improved the eGFR accuracy (RMSE, 15.00 mL/min; 95% CI, 14.12 to 16.00 mL/min) compared with all published models. Body surface area (BSA)–adjusted CKD-EPI was the most accurate published model for eGFR (RMSE, 16.30 mL/min; 95% CI, 15.34 to 17.38 mL/min). Importantly, the new model reduced the fraction of patients with a carboplatin dose absolute percentage error > 20% to 14.17% in contrast to 18.62% for the BSA-adjusted CKD-EPI and 25.51% for the Cockcroft-Gault formula. The results were externally validated. The online tool for our model has had 1200 unique users in the first 6 weeks since online publication.

Conclusion

The new model improves this estimation and may present a new standard of care. Further improvements can be achieved with purpose build models that investigate best dose calculations for specific indications, such as adjuvant treatment of patients with seminoma. 1) Janowitz and Williams et al., doi:10.1200/JCO.2017.72.7578