PMID- 27511905 OWN - NLM STAT- MEDLINE DCOM- 20171101 LR - 20191210 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 21 IP - 10 DP - 2016 Oct TI - Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma. PG - 1218-1229 AB - 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. CI - (c)AlphaMed Press. FAU - Lacouture, Mario E AU - Lacouture ME AD - Memorial Sloan Kettering Cancer Center, New York, New York, USA LacoutuM@mskcc.org. FAU - Dreno, Brigitte AU - Dreno B AD - Department of Dermatology, Hotel Dieu University Hospital, Nantes, France. FAU - Ascierto, Paolo Antonio AU - Ascierto PA AD - Istituto Nazionale Tumori Fondazione, G Pascale, Naples, Italy. FAU - Dummer, Reinhard AU - Dummer R AD - University of Zurich Hospital, Zurich, Switzerland. FAU - Basset-Seguin, Nicole AU - Basset-Seguin N AD - Universite Paris 7 and Hopital Saint-Louis, Paris, France. FAU - Fife, Kate AU - Fife K AD - Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom. FAU - Ernst, Scott AU - Ernst S AD - Western University London Regional Cancer Program, London, Ontario, Canada. FAU - Licitra, Lisa AU - Licitra L AD - Fondazione IRCCS, Istituto Tumori, Milan, Italy. FAU - Neves, Rogerio I AU - Neves RI AD - Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. FAU - Peris, Ketty AU - Peris K AD - Catholic University of Rome, Rome, Italy. FAU - Puig, Susana AU - Puig S AD - Dermatology Department, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain. FAU - Sokolof, Jonas AU - Sokolof J AD - Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Sekulic, Aleksandar AU - Sekulic A AD - Mayo Clinic, Scottsdale, Arizona, USA. FAU - Hauschild, Axel AU - Hauschild A AD - Department of Dermatology, University of Kiel, Kiel, Germany. FAU - Kunstfeld, Rainer AU - Kunstfeld R AD - Medical University of Vienna, Vienna, Austria. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R01 CA083115/CA/NCI NIH HHS/United States PT - Journal Article PT - Review DEP - 20160810 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Anilides) RN - 0 (Antineoplastic Agents) RN - 0 (Biphenyl Compounds) RN - 0 (Hedgehog Proteins) RN - 0 (HhAntag691) RN - 0 (Pyridines) RN - 0RLU3VTK5M (sonidegib) SB - IM MH - Alopecia/chemically induced MH - Anilides/*adverse effects MH - Antineoplastic Agents/*adverse effects MH - Asthenia/chemically induced MH - Biphenyl Compounds/*adverse effects MH - Carcinoma, Basal Cell/*drug therapy MH - Hedgehog Proteins/*antagonists & inhibitors/physiology MH - Humans MH - Pyridines/*adverse effects MH - Signal Transduction/drug effects MH - Spasm/chemically induced MH - Taste Disorders/chemically induced MH - Weight Loss/drug effects PMC - PMC5061532 OTO - NOTNLM OT - Advanced basal cell carcinoma OT - Adverse events OT - Hedgehog pathway OT - Management OT - Sonidegib OT - Vismodegib EDAT- 2016/08/12 06:00 MHDA- 2017/11/02 06:00 PMCR- 2017/04/01 CRDT- 2016/08/12 06:00 PHST- 2016/05/08 00:00 [received] PHST- 2016/06/09 00:00 [accepted] PHST- 2016/08/12 06:00 [pubmed] PHST- 2017/11/02 06:00 [medline] PHST- 2016/08/12 06:00 [entrez] PHST- 2017/04/01 00:00 [pmc-release] AID - theoncologist.2016-0186 [pii] AID - T16186 [pii] AID - 10.1634/theoncologist.2016-0186 [doi] PST - ppublish SO - Oncologist. 2016 Oct;21(10):1218-1229. doi: 10.1634/theoncologist.2016-0186. Epub 2016 Aug 10.