Baseline GFR and cisplatin-induced renal toxicity in urothelial cancer patients.

Abstract

380 Background: Cisplatin eligibility for clinical trials has been defined as calculated GFR > 60 mL/min due to risk of nephrotoxicity in patients (pts) with renal impairment. For urothelial cancer (UCa), substitution of cisplatin compromises outcomes. We evaluated change in GFR in pts treated with cisplatin despite baseline GFR < 60 to determine risk of nephrotoxicity. Methods: 150 USC pts were identified who received systemic therapy for UCa from 2009 to 2014. Creatinine and weight values closest to treatment start and finish were used for calculation of GFR using the Cockcroft-Gault formula. Wilcoxon rank-sum tests and analyses of variance (ANOVA) were used to compare GFR percent change by age ( < 75 vs > 75 years), pre-treatment GFR ( < 60 vs > 60), therapy setting (neoadjuvant, adjuvant, or metastatic), primary disease site, and comorbidities (diabetes, hypertension, hyperlipidemia). Log-rank tests and Cox regression models were used to examine the association between overall survival (OS) and age or GFR. Results: 114 received cisplatin-based therapy at least once; 26 in the neo-adjuvant setting, 27 adjuvant, and 61 for metastatic disease. GFR could be calculated pre- and post-treatment for 81 pts; lowest GFR in pt receiving cisplatin was 25.5 mL/min. Median GFR change was -1.6% (range: -50% ~ 49%) for pts with pre-treatment GFR < 60 compared to -10.9% (range -72%, 135%) for pts with pre-treatment GFR > 60 (p = 0.17). Treatment setting (neo-adjuvant, adjuvant, or metastatic) had significant association with GFR change (p = 0.027). Median (range) of GFR change for the neo-adjuvant setting, adjuvant setting and metastatic setting was 4.6% (95% CI -32%, 90%), -5.8% (95% CI-39%, 20%), -11.9% (95% CI -72%, 135%), respectively. Age, primary disease site, diabetes, hypertension and hyperlipidemia were not associated with GFR change. Univariate analysis showed an association between GFR > 60 at stop of treatment with worse OS (p = 0.087) in metastatic pts. Conclusions: Our data support the hypothesis that UCa pts with GFR < 60 do not experience a greater decline in renal function after cisplatin treatment compared to patients with GFR > 60. If validated, this may extend the option of cisplatin-based therapy to previously ineligible pts.