Hao Zhenghua, Yu Linglu
Department of Pharmacy, Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, 030001, China.
School of Integrative Medicine, Nanjing University of Chinese Medicine, Qixia District, No. 138, Xianlin Road, Nanjing, 210023, China.
Int J Clin Pharm. 2025 Aug 28. doi: 10.1007/s11096-025-01994-0.
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.
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.
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.
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.
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.
丝裂霉素是一种细胞毒性抗肿瘤抗生素，已被批准用于治疗低度上尿路尿路上皮癌（UTUC）和非肌层浸润性膀胱癌（NMIBC）。它还被用于眼科手术和胃肠道恶性肿瘤的非适应证用药。尽管丝裂霉素的疗效已得到广泛认可，但其安全性，尤其是关于罕见或严重不良事件（AE），在大型真实世界人群中的特征仍未得到充分描述。
本研究旨在通过对两个主要的全球药物警戒数据库进行综合分析，评估丝裂霉素相关的不良事件，以识别高风险器官系统和需要提高临床关注度的特定AE信号。
从美国食品药品监督管理局不良事件报告系统（FAERS）中检索2004年第一季度至2024年第三季度的AE数据。根据医学术语词典（MedDRA）术语对数据进行去重和标准化处理。从世界卫生组织VigiAccess数据库收集补充数据。使用四种信号检测算法进行不成比例分析：报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项伽马泊松收缩器（MGPS）。使用非参数统计方法分析不良事件的发病时间。
在FAERS数据库中，共识别出1461份与丝裂霉素相关的报告，包括3652例AE。值得注意的是，在系统器官分类（SOC）层面，眼部、肾脏和泌尿系统、血液和淋巴系统以及皮肤和皮下组织疾病出现了强烈的安全信号。在首选术语（PT）层面，观察到严重事件的不成比例值较高，如巩膜变薄（OR = 7129.60，95% CI 4576.64 - 11106.7）和膀胱穿孔（OR = 1585.69，95% CI 1111.91 - 2261.33）。超过三分之二的AE发生在给药后30天内，尽管68.93%的报告缺乏有效的发病时间数据。VigiAccess的研究结果证实了FAERS中观察到的SOC趋势。
丝裂霉素与广泛的器官特异性毒性相关，其中许多毒性在治疗过程早期出现，可能具有严重的临床后果。本研究强调了在接受丝裂霉素治疗的人群中进行早期风险识别、个体化监测策略以及加强药物警戒的必要性。这些发现为优化丝裂霉素在肿瘤学和其他治疗环境中的安全有效使用提供了重要基础。
