Abstract
Systemic chemotherapy plays a central role in the management of metastatic bladder cancer. Although responses may be observed initially, overall survival with multiagent chemotherapy is still limited. No significant improvements have been made by novel cytotoxic or targeted agents in last decade. There exists an urgent need for the development of novel therapeutic agents to improve outcomes for these patients. In this paper, we review the role of immunotherapy, the programmed death 1 (PD-1) receptor and its ligands (PD-L1/2), and ongoing drug development efforts to block this pathway in bladder cancer, focusing on the currently available data from ongoing clinical trials.
Highlights
Bladder cancer is the most common malignant disease involving the urinary system
We review the role of immunotherapy, the programmed death 1 (PD-1) receptor and its ligands (PD-L1/2), and ongoing drug development efforts to block this pathway in bladder cancer, focusing on the currently available data from ongoing clinical trials
Immune monitoring studies of patients with bladder cancer who were treated with two cycles of preoperative ipilimumab, have shown that treatment with anti–Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) antibody leads to an increase in the population of CD4+ inducible costimulator cells (CD4+ICOShi) in both tumor tissues and peripheral blood (Carthon et al, 2010)
Summary
Bladder cancer is the most common malignant disease involving the urinary system. Approximately 74,690 patients will be diagnosed with bladder cancer in 2014 ("SEER Stat Fact Sheets: Bladder Cancer", 2014). Other intravesical agents have been evaluated in superficial bladder cancer, but none has proven to be more effective than BCG. Treatment with ipilimumab significantly increases median overall survival in both previously untreated and treated patients with metastatic melanoma (Hodi et al, 2010). Immune monitoring studies of patients with bladder cancer who were treated with two cycles of preoperative ipilimumab, have shown that treatment with anti–CTLA-4 antibody leads to an increase in the population of CD4+ inducible costimulator cells (CD4+ICOShi) in both tumor tissues and peripheral blood (Carthon et al, 2010). Ipilimumab is currently being evaluated in a Phase II study in combination with cisplatin and gemcitabine for advanced urothelial cancer ("Phase II Trial of Gemcitabine, Cisplatin, Plus Ipilimumab as First-line Treatment for Patients With Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU10-148")
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