PO.CL11.01 · 临床研究
接受小分子抑制剂治疗的癌症患者的脱发：来自临床试验的证据
Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
脱发仍是癌症治疗最常见且最令人痛苦的副作用之一。虽然传统上与细胞毒性化疗相关，但越来越多的证据表明，靶向FGFR、BRAF和Src/ABL等通路的小分子抑制剂也可诱发临床上显著的脱发。然而，在小分子抑制剂单药治疗中，发病率和严重程度模式仍未得到充分表征。我们对PubMed和Embase进行了范围综述，以识别报告接受小分子治疗的癌症患者脱发情况的临床试验。合格的药物包括激酶抑制剂（如BRAF、KIT、FGFR、多激酶、Hedgehog通路）和激素类药物。若研究包含临床前研究、病例报告、病例系列、综述或生物疗法，则予以排除。提取脱发发病率、严重程度和临床表现的数据，并跨小分子药物类别进行定性综合。本综述纳入了18项临床试验，脱发发病率范围为9%至63%。Hedgehog通路抑制剂诱发的总体发生率最高，saridegib和glasdegib为20-30%，vismodegib高达63%。FGFR抑制剂（pemigatinib、infigratinib）和其他激酶抑制剂（ripretinib、vemurafenib、sorafenib、AZD0424）显示中等发生率（22-48%）。芳香化酶抑制剂（anastrozole、lenostrozole）和aurora B激酶抑制剂BI 811283的脱发发病率较低，为9至21%。在这些单药治疗中，脱发主要为1-2级，3级或以上脱发发生于不到1%的患者。尽管脱发事件为低级别，但其社会心理影响仍很显著。Hedgehog抑制剂相比芳香化酶抑制剂所见的较高发生率，凸显了通路特异性的毛囊信号传导破坏如何促成脱发。进一步研究这些药物的分子机制可能有助于临床医生更好地预测和管理这一副作用。
查看英文原文 English abstract
Alopecia remains one of the most common and distressing side effects of cancer therapy. While traditionally associated with cytotoxic chemotherapy, increasing evidence shows that small molecule inhibitors, targeting pathways such as FGFR, BRAF, and Src/ABL, can also induce clinically significant hair loss. However, incidence and severity patterns remain poorly characterized across small molecule inhibitor monotherapy. A scoping review of PubMed and Embase was conducted to identify clinical trials reporting alopecia in cancer patients treated with small molecule therapies. Eligible agents included kinase inhibitors (e.g., BRAF, KIT, FGFR, multikinase, Hedgehog pathway) and hormonal agents. Studies were excluded if they comprised preclinical studies, case reports, case series, reviews, or biologic therapies. Data on alopecia incidence, severity, and clinical presentation were extracted and synthesized qualitatively across small molecule drug classes. Eighteen clinical trials were included in this review, with alopecia incidence ranging from 9% to 63%. Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%. Across these monotherapies, alopecia was predominantly grade 1-2, with grade 3 alopecia or above occurring in less than 1% of patients. Although alopecia events were low-grade, their psychosocial impact remains significant. The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect.
利益披露 Disclosure
I. Kamholtz, None..
S. I. Gaumond, None.