The continuing role of chemotherapy in the management of advanced urothelial cancer

Abstract

Despite intense drug development in the last decade in metastatic urothelial carcinoma and the incorporation of novel compounds to the treatment armamentarium, chemotherapy remains a key treatment strategy for this disease. Platinum-based combinations are still the backbone of first-line therapy in most cases. The role of chemotherapy in the second line has been more ill-defined due to the complexity of this setting, where patient selection remains critical. Nevertheless, two regimens, one in monotherapy (i.e. vinflunine) and one in combination with antiangiogenics (i.e. docetaxel + ramucirumab) have shown efficacy. Immunotherapy through checkpoint inhibition has revealed remarkably durable benefit in a small proportion of patients in the first and second line and is currently the preferred partner for combinations with chemotherapy. Difficult populations such as patients with liver metastases or those progressing to checkpoint inhibition represent a medical challenge and selective ways of delivering cytotoxics, like the antibody–drug conjugates, might represent a valid alternative. This article reviews the current role of chemotherapy in the management of advanced urothelial carcinoma and the ongoing and coming studies involving this treatment strategy.

Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

“…For more than three decades, no progress has been made in advanced UC therapeutics [ 8 ]. Yet, the recent incorporation of immunotherapy with the arrival to the clinic of the check-point inhibitors has reshaped the treatment scenario, and both atezolizumab (an anti-PD-L1) and pembrolizumab (an anti-PD-1) have become standard options for patients with advanced UC with either progression beyond first-line chemotherapy or treatment naïve and unfit to receive cisplatin [ 19 ].…”

“…These patients can only receive alternative regimens, such as carboplatin, or other regimes with inferior outcomes to cisplatin [ 6 , 7 ]. Second, nearly all patients with metastatic disease, regardless of their response to first-line treatment, will end up progressing and the classic chemotherapy agents explored in the second line have historically provided scarce benefit with an ORR of less than 10%, a short duration of response (DoR) and a median OS of about 7 months [ 8 ]. Therefore, defining a better treatment for cisplatin-unfit patients and improving poor outcomes in the second-line setting are unmet needs.…”

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer

“…Moreover, 50%-70% patients with non-muscle-invasive bladder cancer (NMIBC) will suffer a relapse following transurethral resection, while approximately 30% will progress into muscle-invasive bladder cancer (MIBC), mainly causing UBC-specific deaths 3 . Both doxorubicin (DOX/ADM/ADR) and cisplatin (CIS/DDP/CDDP) have been the first-line chemotherapy drugs effectively against UBC, but the high rates of DOX- and CIS- chemoresistance in recurrent UBC remain a major barrier to improve the prognosis of patients 4 , 5 . It still maintains a challenge to explore novel effective chemotherapeutic agents for the treatment of drug-resistant UBC.…”

Cell Therapies in Bladder Cancer Management

“…This treatment is highly aggressive and, due to other comorbidities associated with advanced age, in some cases, it cannot be used and only in few situations leads to complete pathological responses. Moreover, MIBC relapse and progression to metastatic disease occurs often and is associated with poor prognosis, and adjuvant chemotherapy only shows minor increases in patient survival [ 7 ]. All these clinical characteristics make perioperative immunotherapy an attractive option to be offered in clinical trial settings.…”