Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

Autor: Nicole Basset-Seguin, Aleksandar Sekulic, Scott Ernst, Rogerio I. Neves, Kate Fife, Axel Hauschild, Paolo A. Ascierto, Brigitte Dréno, Reinhard Dummer, Rainer Kunstfeld, Susana Puig, Lisa Licitra, Ketty Peris, Jonas Sokolof, Mario E. Lacouture
Přispěvatelé: University of Zurich, Lacouture, Mario E
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Cancer Research
Spasm
Advanced basal cell carcinoma
Adverse events
Hedgehog pathway
Management
Sonidegib
Vismodegib
Pyridines
chemistry.chemical_compound
Taste Disorders
1306 Cancer Research
Anilides
10177 Dermatology Clinic
Hedgehog signaling pathway
3. Good health
Biphenyl compound
Taste disorder
2730 Oncology
medicine.symptom
Settore MED/35 - MALATTIE CUTANEE E VENEREE
medicine.drug
Signal Transduction
medicine.medical_specialty
610 Medicine & health
Antineoplastic Agents
03 medical and health sciences
Internal medicine
Weight Loss
medicine
Humans
Basal cell carcinoma
Hedgehog Proteins
Adverse effect
business.industry
Biphenyl Compounds
Alopecia
medicine.disease
Surgery
Dysgeusia
030104 developmental biology
chemistry
Carcinoma
Basal Cell
Asthenia
Melanoma and Cutaneous Malignancies
business
Zdroj: The Oncologist
ISSN: 1549-490X
Popis: 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. Implications for Practice: 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.
Databáze: OpenAIRE
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