Real-world safety profile of mitomycin: signal detection and time-to-onset analysis from FDA adverse event reporting system and VigiAccess databases.

Introduction: Mitomycin, a cytotoxic antitumor antibiotic, has been approved for the treatment of low-grade upper tract urothelial carcinoma (UTUC) and non-muscle invasive bladder cancer (NMIBC). It is also used off-label in ophthalmic procedures and gastrointestinal malignancies. Although the efficacy of mitomycin is well recognized, its safety profile, particularly regarding rare or serious adverse events (AEs), remains insufficiently characterized in large real-world populations.

Aim: This study aimed to evaluate mitomycin-associated AEs through comprehensive analysis of two major global pharmacovigilance databases, with the goal of identifying high-risk organ systems and specific AE signals requiring increased clinical awareness.

Method: AE data were retrieved from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q3 2024. Data were deduplicated and standardized according to MedDRA terminology. Complementary data were collected from the World Health Organization VigiAccess database. Disproportionality analysis was performed using four signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time-to-onset of adverse events was analyzed using non-parametric statistical methods.

Results: A total of 1461 mitomycin-related reports, comprising 3652 AEs, were identified in the FAERS database. Notably, strong safety signals have emerged at the system organ class (SOC) level for eye, renal and urinary, blood and lymphatic system, and skin and subcutaneous tissue disorders. At the preferred term (PT) level, high disproportionality values were observed for serious events, such as scleral thinning (OR = 7129.60, 95% CI 4576.64-11,106.7) and bladder perforation (OR = 1585.69, 95% CI 1111.91-2261.33). Over two-thirds of AEs occurred within 30 days of drug administration, although 68.93% of the reports lacked valid onset-time data. The VigiAccess findings corroborated the SOC trends observed in FAERS.

Conclusion: Mitomycin is associated with a broad range of organ-specific toxicities, many of which occur early in the treatment course and may have serious clinical consequences. This study highlights the need for early risk identification, individualized monitoring strategies, and greater pharmacovigilance in populations treated with mitomycin. These findings provide an important foundation for optimizing the safe and effective use of mitomycin in oncology and in other therapeutic settings.