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  • Reliability of estimated glomerular filtration rate in patients treated with platinum containing therapy.

Reliability of estimated glomerular filtration rate in patients treated with platinum containing therapy.

International journal of cancer (2014-03-04)
Jakob Lauritsen, Maria G Gundgaard, Mette S Mortensen, Peter S Oturai, Bo Feldt-Rasmussen, Gedske Daugaard
ABSTRACT

Estimates of glomerular filtration rate (eGFR) are widely used when administering nephrotoxic chemotherapy. No studies performed in oncology patients have shown whether eGFR can safely substitute a measured GFR (mGFR) based on a marker method. We aimed to assess the validity of four major formulas based on PCr (Cockcroft-Gault, MDRD, Wright and CKD-EPI) in comparison to mGFR in an oncology setting. Patients included had disseminated germ cell cancer and received conventional chemotherapy: bleomycin, etoposide and cisplatin. The mGFR of the patients was compared to all estimates with focus on bias (median percentage error), precision (median absolute percentage error) and accuracy (p10 and p30). The precision of carboplatin dosage based on eGFR was calculated. Data on mGFR, eGFR, and PCr were available in 390 patients, with a total of ∼ 1,600 measurements. Median PCr and mGFR synchronically decreased after chemotherapy, yielding high bias and low precision of most estimates. Post-chemotherapy, bias ranged from -0.2% (MDRD after four cycles) to 33.8% (CKD-EPI after five cycles+), precision ranged from 11.6% (MDRD after four cycles) to 33.8% (CKD-EPI after five cycles+) and accuracy (p30) ranged from 37.5% (CKD-EPI after five cycles+) to 86.9% (MDRD after four cycles). Although MDRD appeared acceptable after chemotherapy because of high accuracy, this equation underestimated GFR in all other measurements. Before and years after treatment, Cockcroft-Gault and Wright offered best results. Precision of carboplatin dosage was low. In conclusion, bias, precision and accuracy were unacceptable in all equations due to a synchronous decrease of PCr and mGFR during chemotherapy.

MATERIALS
Product Number
Brand
Product Description

Bleomycin sulfate, European Pharmacopoeia (EP) Reference Standard
Etoposide for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
Sigma-Aldrich
Bleomycin sulfate from Streptomyces verticillus, for fluorescence, mixture of bleomycin sulfate salts, lyophilized, powder or crystals, white to off-white
Sigma-Aldrich
Carboplatin
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
Etoposide, synthetic, 95.0-105.0%, powder
Sigma-Aldrich
Bleomycin sulfate from Streptomyces verticillus, 1.5-2.0 units/mg solid, BioReagent, suitable for cell culture
Sigma-Aldrich
Creatinine, anhydrous, ≥98%
Sigma-Aldrich
Bleomycin sulfate from Streptomyces verticillus, BioXtra, crystalline
Sigma-Aldrich
Bleomycin sulfate from Streptomyces verticillus, crystalline, 1.5-2.0 U/mg
Etoposide, European Pharmacopoeia (EP) Reference Standard
Cisplatin, European Pharmacopoeia (EP) Reference Standard