Abstract
Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.
Highlights
Cytotoxic chemotherapy has been the mainstay of medical therapy for patients with metastatic urothelial cancer (UC) for a long time
One clinical trial comparing a gemcitabine-plus-cisplatin regimen (GC) with MVAC demonstrated that the GC regimen had a treatment efficacy similar to that of MVAC while causing less toxicity than MVAC [2, 3]
We provide a brief overview of these immune-checkpoint inhibitors and a summary of comprehensive medical treatment using cytotoxic chemotherapy for metastatic UC, including ongoing clinical trials
Summary
Cytotoxic chemotherapy has been the mainstay of medical therapy for patients with metastatic urothelial cancer (UC) for a long time. Durvalumab is currently being tested in a phase III international, multi-institutional clinical trial to compare durvalumab monotherapy, a combination of durvalumab and tremelimumab (AstraZeneca), a fully human monoclonal antibody against anti-CTLA-4, and standard chemotherapy as first-line therapy for patients with previously untreated advanced UC. Severe (grade 3–4) treatment-related AEs included anemia (18%), thrombocytopenia (23%), and neutropenia (52%) including febrile neutropenia (11%), whereas non-hematologic toxicity was rare [13] These immune-checkpoint inhibitors have led to breakthroughs in medical therapy for patients with metastatic UC, cytotoxic chemotherapy is still the standard firstline therapy. As described above, on current, various clinical trials, which is comparing immune-checkpoint inhibitors monotherapy and combination of immune-checkpoint inhibitors with standard chemotherapy as first-line therapy for patients with advanced UC Expression level of these drug function and/or resistance associated genes might become one of the key factors whether we decide to undergo checkpoint inhibitors monotherapy or combination therapy with cytotoxic chemotherapy. As more treatment options become available, more biomarkers need to be established
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