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

Lacouture, Mario E.; Dréno, Brigitte; Ascierto, Paolo A.; Dummer, Reinhard; Basset-Séguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulić, Aleksandar; Hauschild, Axel; Kunstfeld, Rainer

doi:10.1634/theoncologist.2016-0186

Cited by 138 publications

(136 citation statements)

References 70 publications

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“…The treatment of muscle spasms with amlodipine (up to 10 mg daily), gabapentin (300-900 mg daily), pregabalin (varies with symptoms and causes), or cyclobenzaprine (5-10 mg 3 times daily) have been reported [33]. Nausea and vomiting might be treated with scopolamine given transdermally at 1.5 mg every 3 days as has been previously reported [33].…”

Section: Discussionmentioning

confidence: 83%

“…Moreover, although the Using effective techniques to manage AEs may help improve QoL for those patients who experience decreased QoL because of their treatment. For example, treating weight loss and dysgeusia may involve consultation with a dietitian, alopecia may be treated with 5% minoxidil twice daily or finasteride (1 mg daily for men; 5 mg daily for women), and diarrhea may be treated with loperamide 2 mg up to 16 mg daily [33]. The treatment of muscle spasms with amlodipine (up to 10 mg daily), gabapentin (300-900 mg daily), pregabalin (varies with symptoms and causes), or cyclobenzaprine (5-10 mg 3 times daily) have been reported [33].…”

Section: Discussionmentioning

confidence: 99%

“…For example, treating weight loss and dysgeusia may involve consultation with a dietitian, alopecia may be treated with 5% minoxidil twice daily or finasteride (1 mg daily for men; 5 mg daily for women), and diarrhea may be treated with loperamide 2 mg up to 16 mg daily [33]. The treatment of muscle spasms with amlodipine (up to 10 mg daily), gabapentin (300-900 mg daily), pregabalin (varies with symptoms and causes), or cyclobenzaprine (5-10 mg 3 times daily) have been reported [33]. Nausea and vomiting might be treated with scopolamine given transdermally at 1.5 mg every 3 days as has been previously reported [33].…”

Section: Discussionmentioning

confidence: 99%

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Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

Migden¹

2017

J Clin Exp Dermatol Res

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Basal cell carcinoma (BCC), the most common form of cancer, affects approximately 2 million people annually in the US. Aberrant activation of the hedgehog signaling pathway plays an important role in BCC. Two inhibitors of the SMO component of hedgehog signaling, vismodegib and sonidegib, are currently approved for use in advanced BCC, including locally advanced BCC (laBCC) and metastatic BCC (mBCC), depending on the country of approval. Location of lesions and fears about changes in appearance may affect the quality of life (QoL) of patients with advanced BCC. In addition, QoL itself is an outcome for advanced BCC. The key clinical trials for vismodegib (ERIVANCE and STEVIE) and for sonidegib (BOLT) included QoL as secondary end points, using different questionnaires for assessment. In ERIVANCE, Short Form-36 for assessing QoL showed no changes from baseline on either the physical or emotional domains. In STEVIE, the Skindex-16 for assessing QoL showed that treatment with vismodegib was associated with clinically meaningful improvement in the emotional domain. To determine QoL, BOLT used predetermined subscales related to skin specifically from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC H&N35. Both the QLQ-C30 and H&N35 selected subscales showed either maintenance or improvement from baseline. Factors affecting QoL during treatment of patients with advanced BCC include baseline QoL, having fewer comorbidites, and having better initial mental health status. In addition, patients whose lesions were advanced, but were not as large as others or not located in visible areas (ie, head and neck) reported better QoL. Treatment-emergent adverse events (AEs) have an impact on QoL in patients with advanced BCC. Most of the AEs reported in trials for vismodegib and sonidegib were grade 1-2. Using techniques to manage AEs effectively may help improve QoL for those whose QoL decreases during treatment.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

Migden¹

2017

J Clin Exp Dermatol Res

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“…4 Muscle cramping is the most commonly reported AE with individual studies estimating that between 60-70% of users experience cramping.…”

Section: Case #1 Case #2mentioning

confidence: 99%

“…Good hydration, gentle exercise, stretching, and massage have been suggested for mild cases of cramping. 4 In more severe cases different pharmacologic treatments have been used with variable effectiveness. Ally et al found modest decreases in cramping within two weeks of starting treatment with calcium channel blockers.…”

Section: Case #1 Case #2mentioning

confidence: 99%

L-Carnitine Reduces Muscle Cramps in Patients taking Vismodegib

et al. 2018

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Vismodegib is a novel oral Smoothened (SMO) antagonist, approved by the Food and Drug Administration (FDA) for the treatment of locally advanced (laBCC) and metastatic (mBCC) basal cell carcinoma. 1Significant therapeutic results are obtained with vismodegib; however, adverse events often limit use to less than the time needed for optimal therapy. The most common side effect of HHIs is muscle cramps, reported in about 60-70% of patients.2,3 Muscle cramps are a frequent source of patient dissatisfaction and often result in a significant negative impact on patient quality of life. We report 3 patients taking vismodegib who experienced a reduction in muscle cramps after starting L-carnitine, a dietary supplement. ABSTRACTVismodegib is an oral, small-molecule hedgehog pathway inhibitor (HHI) approved for the treatment of locally advanced and metastatic basal cell carcinoma. While an effective treatment option for these conditions, HHI therapy is associated with muscle cramps in a significant number of patients. This adverse effect negatively impacts patient quality of life and patient adherence to the prescribed treatment regimen.Levocarnitine (L-carnitine) is a trimethylated amino acid known to play a critical role in lipid metabolism. It has antioxidant properties, and several studies have illustrated its effectiveness in lessening the severity of muscle cramps in various disease processes.We present three patients who developed muscle cramping associated with vismodegib treatment for basal cell carcinoma. Each was started on L-carnitine therapy, and all three reported a significant decrease in the severity of their muscle cramps to the point that they were able to continue HHI therapy without taking a drug holiday. These cases illustrate a promising treatment option for the most common side effect associated with HHI treatment.

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Acquired Disorders of Hair

Harries,

Holmes,

McMichael

et al. 2024

Rook's Textbook of Dermatology

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This chapter reviews acquired hair disorders, including common scarring and non‐scarring alopecia presentations, conditions characterised by excessive body hair growth and acquired hair shaft disorders. We also describe the biology of normal hair follicles, including structure, hair cycle control and immunity, to better understand the mechanisms underlying these conditions. We present methods for clinical assessment, recommended investigation and management of each disease, and present summaries of frequently used therapeutics and cosmetic options employed when treating these problems.

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

Cited by 138 publications

References 70 publications

Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

L-Carnitine Reduces Muscle Cramps in Patients taking Vismodegib

Acquired Disorders of Hair

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