Second-line chemotherapy for advanced and metastatic urothelial carcinoma - Vinflunine and beyond: A comprehensive review of the current literature

To comprehensively review current efforts and advances in the field of chemotherapeutic and biologically targeted treatment options after failure of cisplatin-based first-line regimens in urothelial carcinoma.

We searched MEDLINE, CENTRAL, and abstracts of the American Society of Clinical Oncology and the European Society of Medical Oncology meetings to identify original articles, reviews and retrospective analyses on the second-line treatment of urothelial carcinoma. Articles were included if they reported on prospective phase II / III studies or larger high quality retrospective studies of second-line treatment of urothelial carcinoma.

Although considered a chemosensitive disease, the majority of patients with advanced or metastatic urothelial carcinoma relapse after cisplatin-based first-line treatment. Today, none of the commonly used drugs, i. e. , paclitaxel, carboplatin, and / or gemcitabine, is approved by the FDA for second-line systemic treatment. In Europe, vinflunine plus best supportive care is the only option approved by the EMA with moderate clinical efficacy. However, responses to combined chemotherapy approaches are often better, but associated with remarkable toxicity. In patients, who had responded well to first-line treatment and are thus considered cisplatin-sensitive, re-administration of a platinum-based combination regimen may be an option. Targeted therapies did not play a role in second-line treatmentment of urothelial cancer so far. Immunotherapeutic strategies to target the PD-1 / PD-L1 axis are emerging. In a recent phase I trial evaluating the Programmed death-ligand 1 targeted monoclonal antibody MPDL3280A, a very promising response rate (43%) with good tolerability was achieved, which lead to immediate breakthrough therapy designation by the FDA. Moreover, combining chemotherapy with targeted agents, e. g. weekly paclitaxel and pazopanib, also shows promising activity in this prognostically poor treatment situation.

Response rates and survival after second-line chemotherapy for advanced or metastatic urothelial carcinoma are poor. To improve outcomes of salvage treatment, novel biologically targeted drugs, either monotherapeutically or as part of a combination with conventional cytostatics, are urgently needed.

The Journal of urology. 2015 Sep 24 [Epub ahead of print]

Christoph Oing, Michael Rink, Karin Oechsle, Christoph Seidel, Gunhild von Amsberg, Carsten Bokemeyer

Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology; University Medical Center Eppendorf; Hamburg; Germany.  Department of Urology; University Medical Center Eppendorf; Hamburg; Germany. , Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology; University Medical Center Eppendorf; Hamburg; Germany. , Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology; University Medical Center Eppendorf; Hamburg; Germany. , Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology; University Medical Center Eppendorf; Hamburg; Germany. , Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology; University Medical Center Eppendorf; Hamburg; Germany.

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