Leung Yin, Yip Terry Cheuk-Fung, Wong Grace Lai-Hung, Wong Vincent Wai-Sun, Hui Vicki Wing-Ki, Mok Tony Shu-Kam, Chan Henry Lik-Yuen, Chan Stephen Lam, Lui Rashid Nok-Shun
Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
Cancer Med. 2025 Jan;14(1):e70583. doi: 10.1002/cam4.70583.
Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy.
All patients who had received at least one dose of immune checkpoint inhibitors (ICIs) from July 1, 2014 to October 31, 2019 were identified from Hong Kong's territory-wide database, with this date defined as the baseline. A 1-month landmark analysis was conducted with follow-for up to 6 months, including an exposure period of 1 month before and after the baseline date. Patients were grouped according to the types of primary cancer and the percentages of daily H1-antihistamine usage within the exposure period. The primary outcome was overall survival.
A total of 1740 (65.1% male, mean age 61.9 years) were included in the landmark analysis, of which 529 (30.4%) and 307 (17.6%) had primary lung and liver malignancies. The multivariable Cox regression model estimated statistically significant improvement in overall survival of intermediate use in patients with primary lung malignancies (adjusted hazard ratio [aHR] 0.223, 95% confidence interval [CI] 0.052-0.958, p = 0.044), but not with primary liver maligancies. Similar frequency-dependent effects were identified in Kaplan-Meier analysis.
The benefits of adjunctive use of H1-antihistamines may be generation- and tumor-dependent. Further clinical and mechanistic studies are required to confirm the findings.
近期研究（Li等人，2021年）表明，肿瘤微环境中巨噬细胞上H1受体的表达和激活上调，同时使用H1抗组胺药与接受免疫治疗的肺癌和皮肤癌患者的总生存期改善相关。因此，我们回顾性评估了免疫治疗期间使用H1抗组胺药对癌症患者的影响。
从香港全港数据库中识别出2014年7月1日至2019年10月31日期间接受至少一剂免疫检查点抑制剂（ICI）的所有患者，将该日期定义为基线。进行为期1个月的标志性分析，随访长达6个月，包括基线日期前后各1个月的暴露期。患者根据原发性癌症类型和暴露期内每日使用H1抗组胺药的百分比进行分组。主要结局是总生存期。
共有1740例（男性占65.1%，平均年龄61.9岁）纳入标志性分析，其中529例（30.4%）和307例（17.6%）患有原发性肺癌和肝癌。多变量Cox回归模型估计，原发性肺癌患者中等剂量使用H1抗组胺药可使总生存期有统计学意义的改善（调整后危险比[aHR]为0.223，95%置信区间[CI]为0.052 - 0.958，p = 0.044），但原发性肝癌患者无此效果。在Kaplan-Meier分析中也发现了类似的频率依赖性效应。
辅助使用H1抗组胺药的益处可能因代际和肿瘤而异。需要进一步的临床和机制研究来证实这些发现。
