Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma.
Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma.
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DOI：
10.1634/theoncologist.2016-0186
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Kunstfeld R
中科院分区：
文献类型：
--
作者：
Lacouture ME;Dréno B;Ascierto PA;Dummer R;Basset-Seguin N;Fife K;Ernst S;Licitra L;Neves RI;Peris K;Puig S;Sokolof J;Sekulic A;Hauschild A;Kunstfeld R
Vismodegib和sonidegib是Hedgehog通路抑制剂（HPI），被批准用于治疗晚期基底细胞癌患者。与这些治疗相关的不良事件（AE）可能会因生活质量下降和治疗中止而影响临床结局。本文描述了与HPI给药相关的AE的发生率、临床表现、推定机制和管理策略。hedgehog信号通路的异常激活是基底细胞癌（BCC）发病机制的关键驱动因素。Vismodegib是一类hedgehog通路信号传导的小分子抑制剂，已被监管机构批准用于治疗患有转移性BCC或手术后复发的局部晚期BCC的成人，或者不是手术候选人并且不是放射候选人的人。第二种抑制剂sonidegib最近也被批准用于同一组局部晚期BCC患者。刺猬通路抑制剂（HPI）治疗患者中常见的不良事件（AE）包括肌肉痉挛、味觉丧失/味觉障碍、脱发、体重减轻和虚弱（疲劳）。认为这些AE与正常组织中hedgehog通路的抑制机制相关。尽管大多数与HPI相关的AE的严重程度为1-2级，但这些AE的长期性质可能导致生活质量下降、治疗中断，在某些情况下甚至停药，所有这些都可能影响临床结局。描述了晚期BCC中与HPI相关的AE的发生率、临床表现、推定机制和管理策略。这些意见是朝着制定基于机制的预防和管理战略迈出的第一步。了解这些AE将使医疗保健专业人员能够提供适当的咨询和支持性护理干预，所有这些都将有助于改善生活质量和从治疗中获得最佳获益。hedgehog通路抑制剂（HPI）vismodegib和sonidegib代表了晚期基底细胞癌患者的治疗突破。然而，在接受HP治疗的患者中常见的低级别不良事件（AE）的性质（包括肌肉痉挛、味觉丧失/味觉障碍、脱发、体重减轻和疲乏）可能会因生活质量下降和治疗中止而影响临床结局。描述了与HPI给药相关的AE的发生率、临床表现、推定机制和管理策略，目的是使医疗保健专业人员能够为其患者提供适当的咨询和支持性护理干预。
Vismodegib and sonidegib are Hedgehog pathway inhibitors (HPIs) approved for treatment of patients with advanced basal cell carcinoma. The adverse events (AEs) associated with these therapies can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described in this article. Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1–2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy. The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described, with the goal of enabling health care professionals to provide appropriate counseling and supportive care interventions to their patients.
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影响因子：
2.7
作者：
Chiang, C;Swan, RZ;Dlugosz, AA
通讯作者：
Dlugosz, AA
DOI：
10.1038/nrc2503
发表时间：
2008-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
50.5
作者：
Brisbois, T. D.;de Kock, I. H.;Wismer, W. V.
通讯作者：
Wismer, W. V.
影响因子：
--
作者：
BALTODANO, N;GALLO, BV;WEIDLER, DJ
通讯作者：
WEIDLER, DJ
影响因子：
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作者：
Brennan, Donna;Chen, Xiaole;Cheng, Lan;Mahoney, My;Riobo, Natalia A.
通讯作者：
Riobo, Natalia A.