Adverse events associated with cyclophosphamide: A pharmacovigilance study using the FDA adverse event reporting system

Abstract

Objective Cyclophosphamide(CHOP) is a widely used chemotherapeutic agent belonging to the class of alkylating agents. It primarily inhibits the proliferation of tumor cells by interfering with DNA replication and transcription. CHOP has been approved for the treatment of various types of malignant tumors. The aim of this research is to assess adverse events linked to CHOP using real-world data. Methods This research collected and analyzed adverse event reports associated with CHOP from the FAERS(US Food and Drug Administration Adverse Event Reporting System) database spanning from the first quarter of 2004 to the third quarter of 2024. This study leveraged the FAERS database, extracting reports submitted exclusively by healthcare professionals where CHOP was designated as the primary suspect (PS). Four risk signal detection methods were employed: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multiitem Gamma Poisson Shrinker (MGPS), to conduct a comprehensive analysis of CHOP-related ADRs. Results A total of 3,625 adverse event reports with CHOP as the primary suspect drug were obtained. Across 25 system organ classes (SOCs), four positive Preferred Terms(PTs) signals were detected. The most significant signal in SOCs was “blood and lymphatic system disorders” (ROR = 6.64, 95% CI 6.49–6.79), while the most significant PTs signal was “high grade B-cell lymphoma Burkitt-like lymphoma recurrent” (ROR = 613.63, 95% CI 123.85–3040.40). Conclusion This study provides compelling evidence of the presence of CHOP seven unexpected off-label AEs were also observed, such as mucoepidermoid carcinoma, hypotelorism of orbit, breakthrough COVID-19, airway remodeling, meningitis enteroviral, acute graft versus host disease, and gastrosplenic fistula. Additionally, the combination of CHOP and radiotherapy increased the risk of several severe AEs, such as hemorrhagic cystitis. These findings highlight the importance of caution when prescribing CHOP to high-risk individuals with a history of meningitis, cystitis or airway obstruction.