Mitomycin C: New Strategies to Improve Efficacy of a Well-Known Therapy

Abstract

Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably the most commonly used agent given its low rate of side effects and its efficacy. Both the American Urologic Association (AUA) and European Association of Urology (EAU) consider MMC as a standard treatment for immediate single-dose postoperative treatment and for adjuvant therapy in low and intermediate-risk NMIBC. Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered and the schedule widely used is empirical. 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 an optimization of standard MMC therapy or with a combination of MMC with other agents that have different mechanisms of action. Strategies to enhance passive delivery of MMC have been well studied and multiple measures are recommended for implementation of use in routine clinical practice. A modified scheme of instillation seems to be an easy and inexpensive alternative to increase efficacy of intravesical MMC and to also use this agent with an ablative intent. Enhancing tumor response with a sequential therapy is another option that has been investigated, mostly for chemo-immunotherapy wherein the different mechanisms of action of Bacillus of Calmette and Guerìn (BCG) and MMC are combined to achieve a higher response.