title: Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer.
abstract: Nearly three-quarters of all newly diagnosed urothelial cancers are non-muscle-invasive bladder cancers (NMIBCs). Although bladder-preserving surgery can be used to treat NMIBC, the rate of recurrence remains high. Intravesical chemotherapy has been shown to reduce the rate of NMIBC recurrence, and mitomycin C (MMC) has become the most commonly used intravesical cytotoxic agent. Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered. Strategies to enhance delivery of MMC have been well studied and multiple measures are recommended for implementation in routine clinical practice. In addition, less widely investigated techniques, such as hyperthermia and electromotive drug administration, have been shown to increase the efficacy of MMC therapy. Nevertheless, even when the current 'optimal' approaches to MMC administration are used, a large proportion of NMIBCs recur. This apparent treatment resistance might be overcome by combination of MMC with other agents that have different mechanisms of action and are unlikely to have cross-resistance. Study of the mechanisms of resistance is, therefore, important to identify key pathways underlying this phenomenon, which could be rationally targeted using specific combinations of drugs. Knowledge of these mechanisms might also reveal markers of responsiveness to therapy that could be used for patient selection.
authors.affiliation: Department of Urology, Center for Robotic and Laparoscopic Surgery, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Zargar
authors.affiliation: Department of Urology, Bristol Urological Institute, Southmead Hospital, Bristol BS10 5NB, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aning
authors.affiliation: Departments of Surgery and Urology, Austin Health, 145 Studley Road, Heidelberg, Melbourne, VIC 3084, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ischia
authors.affiliation: Department of Urological Sciences, Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: So
authors.affiliation: Department of Urological Sciences, Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Black
mesh_terms: D000283:Administration, Intravesical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage*; D009361:Neoplasm Invasiveness; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin