Impact of renal function of patients with advanced urothelial cancer on eligibility for first-line chemotherapy and treatment outcomes

Objective: The aim of the study is to clarify the clinical effects of first-line chemotherapy regimens for advanced urothelial cancer on clinical responses and survival of patients grouped by renal function. Methods: In this multicenter retrospective cohort study, 345 urothelial cancer patients received systemic chemotherapy for metastatic or unresectable disease in 17 centers (2004-10). Results: Two hundred and forty-one patientswere treatedwithmethotrexate, vinblastine, doxorubicin and cisplatin/methotrexate, epirubicin and cisplatin (n = 136) or gemcitabine and cisplatin (n = 105) followed by carboplatin-based treatments, non-platinum treatments or other regimens. After 2008, gemcitabine and cisplatin was the most frequently used regimen in patients with an estimated glomerular filtration rate < 60 ml/min/1.73 m² and in those with estimated glomerular filtration rate ≥60 ml/ min/1.73 m². The gemcitabine and cisplatin patients' complete response rate was 10.5% and their response ratewas 52.4%, whichwas highest among all regimens. Gemcitabine and cisplatin demonstrated a better 3-year overall survival when the estimated glomerular filtration rate was ≥60 ml/min/ 1.73 m² (31.4%), but it tended to be worse when the estimated glomerular filtration rate was < 60 ml/ min/1.73 m² (14.1%). In the latter cases, the dose reduction rate of gemcitabine and cisplatinwas high (43.9%). Among the patients with estimated glomerular filtration rate < 60 ml/min/1.73 m², the 1-year overall survival of the patients treated with a reduced dose of gemcitabine and cisplatin was significantly lower than that of those treated with standard-dose gemcitabine and cisplatin (26.2 vs. 60.3%, respectively, P = 0.0108). Conclusions: Gemcitabine and cisplatin provided favorable responses and survival in patients with estimated glomerular filtration rate <60 ml/min/1.73 m² but unsatisfactory oncological outcomes in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m², especially when treated with a reduced dose. Alternative regimens might be optimal rather than reduced-dose gemcitabine and cisplatin in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m².