Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang Cancer Hospital, Hangzhou, China.
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Cancer Control. 2024 Jan-Dec;31:10732748241278039. doi: 10.1177/10732748241278039.
Breast cancer has the highest incidence among female malignancies, significantly impacting women's health. Recently, numerous HER2-targeted therapies have achieved excellent clinical outcomes. Currently, anti-HER2 drugs are divided into three main categories: monoclonal antibodies, small-molecule tyrosine kinase inhibitors, and antibody-coupled drugs (ADCs). The main toxic side effects of small molecule TKI-based therapy are diarrhea, hand-foot syndrome, rash, nausea, and vomiting. Diarrhea is a potential predictor of tumor response, affecting up to 95% of cancer patients treated with TKIs. Severe gastrointestinal toxicity can result in the need for dose reductions and treatment interruptions. This not only compromises the efficacy of TKIs but also deteriorates human nutrition and quality of life. The majority of individuals develop diarrhea within 7 days of starting treatment, with approximately 30% developing grade 3 or higher diarrhea within 2-3 days of starting treatment. The severity of diarrhea typically correlates with the dosage of most TKIs. Current prevention and management strategies are primarily empirical, focusing on symptom alleviation rather than addressing the toxicological mechanisms underlying TKI-induced diarrhea. Consequently, anti-diarrheal drugs are often less effective in managing this condition in cancer patients receiving TKIs. Moreover, our understanding of the toxicological mechanisms responsible for such diarrhea remains limited, underscoring the urgent need to identify these mechanisms in order to develop effective anti-diarrheal medications tailored to this specific context. This review aims to elucidate management approaches and mechanisms for diarrhea induced by TKIs during HER2-positive breast cance.
乳腺癌是女性恶性肿瘤中发病率最高的一种，对女性健康有重大影响。最近，许多针对 HER2 的靶向治疗已经取得了良好的临床效果。目前，抗 HER2 药物主要分为三类：单克隆抗体、小分子酪氨酸激酶抑制剂和抗体偶联药物（ADC）。基于小分子 TKI 的治疗的主要毒性副作用是腹泻、手足综合征、皮疹、恶心和呕吐。腹泻是肿瘤反应的潜在预测因素，影响高达 95%接受 TKI 治疗的癌症患者。严重的胃肠道毒性可能导致需要减少剂量和中断治疗。这不仅会影响 TKI 的疗效，还会恶化人类的营养和生活质量。大多数人在开始治疗后 7 天内出现腹泻，约 30%的人在开始治疗后 2-3 天内出现 3 级或更高级别的腹泻。腹泻的严重程度通常与大多数 TKI 的剂量相关。目前的预防和管理策略主要是经验性的，侧重于缓解症状，而不是解决 TKI 引起的腹泻的毒理学机制。因此，在接受 TKI 治疗的癌症患者中，抗腹泻药物通常在管理这种情况时效果不佳。此外，我们对导致这种腹泻的毒理学机制的理解仍然有限，这突显了确定这些机制以开发针对这种特定情况的有效抗腹泻药物的迫切需要。本综述旨在阐明针对 HER2 阳性乳腺癌患者由 TKI 引起的腹泻的管理方法和机制。
