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 . 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 .

Prognostic Value of Pre-operative Renal Insufficiency in Urothelial Carcinoma: A Systematic Review and Meta-Analysis

“…Eighteen studies here 9 13 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 were used to estimate the prevalence of renal insufficiency in patients with UC ( Table 2 ). The prevalence of pre-operative renal insufficiency in UC in this systematic review was 35.9% (ranging from 11.9% to 75.3%).…”

Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways

“…The clinical utility of epirubicin is limited by its dose-dependent toxicity in tissues such as the heart, the liver and the kidney, which lead to reduced antitumor efficacy (Kebieche et al, 2009;Ichioka et al, 2015). Generally, the toxicity in the kidney was attributed to the functional properties of the kidney and the effective elimination of many antineoplastic drugs and their metabolites (Pan et al, 2014).…”

A comparison of nephrotoxicity between patients with a solitary-functioning kidney and those with bilateral-functioning kidneys in cisplatin-based chemotherapy for advanced urothelial carcinoma: A Japanese retrospective multi-institutional study.

“…The effectiveness and the safety of cisplatin dose reduction in patients with pretreatment eGFR < 60 mL/ min/1.73 m 2 has not been clearly elucidated because of the ethical difficulties surrounding conducting such a prospective study [12,24]. Although the one-year overall survival of the patients treated with a reduced dose of cisplatin-based chemotherapy was significantly lower than that of those treated with the standard dose in the CURE study using the same patient series [13], the results of this study demonstrated the safety of cisplatin dose reduction for cisplatin-ineligible patients in preventing nephrotoxicity. Even considering our study results, cisplatin-based chemotherapy is not always safe and is not recommended for all the CKD-S patients with a solitaryfunctioning kidney with pretreatment eGFR < 60 mL/ min/1.73 m 2 .…”

“…Outcomes for cisplatin-eligible advanced UC patients treated with carboplatin-based chemotherapies, such as gemcitabine plus carboplatin, with a median overall survival of 9.0 months, were poorer than those for patients treated with cisplatin-based chemotherapies [6,7]. However, in cisplatin-ineligible advanced UC patients, the median overall survival of patients treated with carboplatin-based combination chemotherapies are reported 7.2-16.3 months [8][9][10][11], which is almost similar (i.e., around 10 months) in those treated with cisplatinbased chemotherapies, including the reduction of cisplatin [12,13] or a split dose of cisplatin regimens [14][15][16].…”