TITLE:
Vismodegib Provides a Novel Treatment for Advanced Basal Cell Carcinoma
AUTHORS:
Jennifer L. Kelm, Thomas J. Magliaro, Matthew L. Anderson, Claire M. Mach
KEYWORDS:
Vismodegib; GDC-0449; Erivedge; Basal Cell Carcinoma
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.2,
February
26,
2014
ABSTRACT: Objective: To review and evaluate vismodegib, the first US
Food and Drug Administration (FDA) approved treatment for locally advanced
(laBCC) or metastatic basal cell carcinoma (mBCC) that has recurred after surgery
or for patients in which surgery or radiation is not an option. Data Sources: A literature search using
PubMed was conducted through January 2013, using the terms vismodegib,
GDC-0449, and Erivedge. Additional literature was found through the reference
citations of identified articles. Study
Selection and Data Extraction: Potential sources were limited to human studies published in English
with a priority placed on those focused on laBCC or mBCC. Data Synthesis: Vismodegib is a selective inhibitor of the
hedgehog (Hh) pathway approved for the treatment of laBCC or mBCC that has
recurred after surgery, or for patients for whom surgery or radiation is
contraindicated. Vismodegib inhibits cancer cell growth and survival by binding
Smoothened, a transmembrane protein involved in the Hedgehog signal
transduction. Vismodegib is administered orally at a dose of 150 mg daily. It
is primarily eliminated through the feces unchanged but does have some
oxidative metabolites produced from the recombinant cytochrome P450 (CYP) 2C9
and CYP3A4/5. Despite CYP450 involvement, it appears to have very few drug
interactions. The most common adverse events reported with vismodegib include
muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, anorexia, and
diarrhea. FDA approval was based on a single arm phase II study that
demonstrated an objective response rate of 30% in mBCC patients and 45% in
laBCC patients. Vismodegib was approved by the FDA on January 30, 2012 for use
in patients with advanced basal cell carcinoma, and continues to be studied in
other patient populations for additional potential uses. Conclusions: Based on a review of current evidence, vismodegib
provides an effective and well-tolerated treatment for otherwise untreatable
basal cell carcinoma.