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

Abstract

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 patients were treated with methotrexate, 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 m(2) and in those with estimated glomerular filtration rate ≥ 60 ml/min/1.73 m(2). The gemcitabine and cisplatin patients' complete response rate was 10.5% and their response rate was 52.4%, which was 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 m(2) (31.4%), but it tended to be worse when the estimated glomerular filtration rate was < 60 ml/min/1.73 m(2) (14.1%). In the latter cases, the dose reduction rate of gemcitabine and cisplatin was high (43.9%). Among the patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), 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 m(2) but unsatisfactory oncological outcomes in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m(2), 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 m(2).

Keywords: chemotherapy; cisplatin; eGFR; gemcitabine; renal function; urothelial cancer.