Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma Journal Article


Authors: Lacouture, M. E.; Dréno, B.; Ascierto, P. A.; Dummer, R.; Basset-Seguin, N.; Fife, K.; Ernst, S.; Licitra, L.; Neves, R. I.; Peris, K.; Puig, S.; Sokolof, J.; Sekulic, A.; Hauschild, A.; Kunstfeld, R.
Article Title: Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma
Abstract: 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 bemechanistically 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-termnature 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. © AlphaMed Press 2016.
Keywords: management; adverse events; hedgehog pathway; vismodegib; advanced basal cell carcinoma; sonidegib
Journal Title: The Oncologist
Volume: 21
Issue: 10
ISSN: 1083-7159
Publisher: Oxford University Press  
Date Published: 2016-01-01
Start Page: 1218
End Page: 1229
Language: English
DOI: 10.1634/theoncologist.2016-0186
PROVIDER: scopus
PUBMED: 27511905
PMCID: PMC5061532
DOI/URL:
Notes: Article -- Export Date: 2 November 2016 -- Source: Scopus
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  1. Mario E Lacouture
    457 Lacouture