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Expert Opin Emerg Drugs. 2014 Sep;19(3):353-65. doi: 10.1517/14728214.2014.914171. Epub 2014 Apr 29.

Emerging drugs and combination strategies for basal cell carcinoma.

Author information

1
University Hospital Zurich, Department of Dermatology , Gloriastrasse 31, CH-8091 Zurich , Switzerland.

Abstract

INTRODUCTION:

Basal cell carcinoma (BCC) is a malignancy that is driven by an activated Hedgehog (Hh) pathway. Smoothened inhibitors are a new promising treatment option for patients with locally advanced or metastatic BCC or basal cell nevus syndrome. But long-term data are still limited, the optimal treatment duration is not yet defined and there are already documented cases with acquired resistance.

AREAS COVERED:

Treatment modalities with Hh inhibitors, side effects and potential pharmacological combination options are discussed. The current literature, including PubMed, Cochrane database and registered trials on ClinicalTrials.gov, was searched.

EXPERT OPINION:

BCCs typically regress during therapy with Hh inhibitors. Muscle toxicity, dysgeusia and hair loss can be considered as on target adverse reactions. Muscle toxicity is the dose-limiting toxicity of sonidegib. It was not seen with vismodegib because of its high binding to plasma protein α-1-acid glycoprotein. Sonidegib is different and shows a clear dose-toxicity relationship, which allows to address the question of whether there is a dose dependency of regression rate, cure rate and progression-free survival. In addition, basic research has offered strategies to enhance efficacy by the combination with other molecules, such as EGFR inhibitors, MEK inhibitors or immunotherapy.

KEYWORDS:

Hedgehog inhibitors; adverse events; basal cell carcinoma; combination therapy; resistance; side effects; smoothened inhibitors; sonidegib; toxic myopathy

PMID:
24773312
DOI:
10.1517/14728214.2014.914171
[Indexed for MEDLINE]

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