The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma

Background: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). Methods: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). Results: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 – 89.0] vs.5.8 [IQR, 2.0 – 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 – 83.3] vs. 5.2 [IQR, 1.7 – 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). Conclusion: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.