Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial

Dréno, Brigitte; Kunstfeld, Rainer; Hauschild, Axel; Fosko, Scott W.; Zloty, David; Labeille, B.; Grob, Jean Jacques; Puig, Susana; Gilberg, Frank; Bergström, Dan; Page, Damian R.; Rogers, Gary S.; Schadendorf, Dirk

doi:10.1016/s1470-2045(17)30072-4

Cited by 178 publications

(195 citation statements)

References 8 publications

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“…This problem could be addressed if alternative, intermittent drug dosing regimens could be considered in patients with low compliance (Dreno et al, 2017). However, this is not an issue for treatments already in the market.…”

Section: Discussionmentioning

confidence: 99%

Vismodegib persistence and discontinuation patterns in Greek patients from a real world setting

Soura

Plaka

Chasapi

et al. 2017

Dermatologic Therapy

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Hedghehog pathway inhibitors have been successfully used for patients with locally advanced basal cell carcinomas. However, these treatments have been associated with various adverse events that may limit patient compliance. In this study, an association of patient and disease characteristics with drug compliance in a real clinical setting was made. 18 patients were included in the study. The average patient age was 78.39 years. The time that patients remained to treatment was, on average, 8.73 months. 72.2% of patients experienced at least one adverse event. At study cut-off, 11 out of 18 patients had discontinued treatment. The most common reason for discontinuation was reported "fatigue" from the treatment due to the type of AEs experienced (37.4%) and patient's choice after complete response achievement (30.8%). Factors that were associated with treatment discontinuation was: number of previous treatments, severity of AEs and patient age.

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Section: Discussionmentioning

confidence: 99%

Vismodegib persistence and discontinuation patterns in Greek patients from a real world setting

Soura

Plaka

Chasapi

et al. 2017

Dermatologic Therapy

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“…Basal cell carcinomas were located on head and neck (45 lesions, 47.9%), upper limbs (19 lesions, 20.2%), trunk (25 lesions, 26.6%) and lower limbs (five lesions, 5.3%). The patients were included in the MIKIE protocol which evaluated the efficacy and tolerability of two treatment regimens of vismodegib in patients with multiple BCCs. Ethics approval was obtained from the Ethics Committee of the University Hospital of Saint‐Etienne.…”

Section: Methodsmentioning

confidence: 99%

“…While surgical excision is the treatment of choice in most cases, new strategies using targeted therapy inhibiting the Hedgehog signalling pathway have been recently developed . In particular, vismodegib has been approved by Food and Drug Administration of the United States of America in 2012 and by the European Medicine Agency in 2013 for metastatic BCC and for locally advanced BCC in patients who are not candidates for either surgery or radiotherapy . Very recently, vismodegib has also been proved to be effective in patients with multiple BCCs …”

Section: Introductionmentioning

confidence: 99%

Reflectance confocal microscopy identification of subclinical basal cell carcinomas during and after vismodegib treatment

Couzan

Cinotti

Labeille

et al. 2017

Acad Dermatol Venereol

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“…9,10 Outside of pharmacologic approaches, some practitioners have found intermittent dosing of vismodegib to lessen cramps, and several trials are underway examining the clinical effectiveness of intermittent dosing. 11,12,13 Levocarnitine (L-carnitine) is a non-essential amino acid that is found in almost all cells, but is concentrated in tissues like skeletal and cardiac muscle that utilize fatty acids as energy. It is naturally produced in the liver and kidneys and can be found in several dietary sources, mainly animal products such as red meat and dairy.…”

Section: Case #3mentioning

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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Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial

Cited by 178 publications

References 8 publications

Vismodegib persistence and discontinuation patterns in Greek patients from a real world setting

Vismodegib persistence and discontinuation patterns in Greek patients from a real world setting

Reflectance confocal microscopy identification of subclinical basal cell carcinomas during and after vismodegib treatment

L-Carnitine Reduces Muscle Cramps in Patients taking Vismodegib

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