Systemic therapy for bladder cancer – a medical oncologist’s perspective

Abstract

Advanced bladder cancer, both muscle-invasive localized disease and metastatic disease, is managed with systemic chemotherapy. Cisplatin-based multi-agent chemotherapy remains the cornerstone for systemic therapy. MVAC (methotrexate-vinblastine-doxorubicin-cisplatin) has been most rigorously studied, both neoadjuvantly and for palliation of metastatic disease. For metastatic disease, cisplatin-gemcitabine (GC) has compared favorably to MVAC due to improved tolerability with similar efficacy. GC has been adopted as standard therapy. Neoadjuvant chemotherapy for muscle-invasive bladder cancer improves survival among those patients eligible to receive cisplatin. Adjuvant chemotherapy is difficult to administer effectively given morbidity of radical cystectomy, and studies have shown mixed results about its benefit. Non-cisplatin regimens have been investigated but remain experimental and reserved for those not candidates for cisplatin in the metastatic setting. While multiple agents have been studied after metastatic disease progression after cisplatin-based therapy, there remain no FDA-approved therapies for the second line. Future trials with anti-VEGF therapy and immunotherapy are actively being investigated. This review examines the systemic therapy available to oncologists with current evidence and future directions.

Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

“…Although most patients with NMIBC generally have favorable outcomes, local therapy with chemotherapy mainly based on mitomycin C often requires repeated treatments [47]. Interestingly, we found that EA enhanced the antiproliferative effects of mitomycin C. These data suggest that also a less aggressive disease might benefit from local or systemic therapy with this compound, possibly reducing the frequency of administration of the chemotherapeutic agent.…”

Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations

“…The overall survival rates are 7% for patients with visceral metastases and 21% for patients without visceral metastases . The evolution of successful targeted therapies for patients with non‐small cell lung cancer and other solid tumors has contrasted significantly with the lack of such approaches reaching regulatory approvals or late‐stage clinical trials for UCB . The purpose of the current study was to expand and validate the identification of CRGAs in a large series of 295 patients with UCB and demonstrate the impact of targeted therapies in selected patients in whom genomically driven treatment was undertaken.…”

“…These successes have led to more rapid drug development and regulatory approvals for targeted therapies for these and other solid tumors and hematolymphoid malignancies . However, for patients with locoregionally advanced and metastatic UCB, targeted therapies have not been approved and patients have limited therapeutic options because chemoresistance to the standard anticancer therapies develops . Thus, there recently has been a growing interest in the development of targeted therapy for UCB .…”

“…10 However, for patients with locoregionally advanced and metastatic UCB, targeted therapies have not been approved and patients have limited therapeutic options because chemoresistance to the standard anticancer therapies develops. 11 Thus, there recently has been a growing interest in the development of targeted therapy for UCB. 12,13 Molecular studies have been performed to determine UCB prognosis over a long period.…”

MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1

“…Its mechanisms of action include the induction of apoptosis of tumor cells by intercalating into their DNA to inhibit its transcription and initiate a DNA damage response (5). DOX-based chemotherapy is used against a wide range of cancer types, including ovarian (6), breast (7) and bladder cancer (8) as well as HCC (9). However, the clinical application of DOX is limited due to cardiac toxicity and drug resistance (10).…”