Purpose: The pharmacology, clinical efficacy, adverse effects, cost, and place in therapy of vismodegib are reviewed.
Summary: Vismodegib, the first oral treatment for basal cell carcinoma (BCC), was recently approved for the treatment of patients with locally advanced or metastatic BCC whose cancer is refractory to standard treatments or who are not candidates for surgery or radiation. Vismodegib is a small molecule that potently inhibits signal transduction in the hedgehog signaling pathway, demonstrates nonlinear pharmacokinetics, and has a half-life of 13 days. Agents that increase gastrointestinal pH may reduce the solubility and bioavailability of vismodegib. It is effective in both locally advanced and metastatic BCCs, with response rates ranging from 30% to 60% in two clinical trials. Vismodegib is available as a 150-mg capsule, and the approved dosage is 150 mg orally once daily. The most common adverse effects of vismodegib include mild-to-moderate hair loss, muscle cramps, taste disturbance, and weight loss. The estimated cost of one month of treatment with vismodegib is $7500.
Conclusion: Vismodegib was recently approved for the treatment of locally advanced or metastatic BCC that is refractory to standard treatments or if patients are not candidates for surgery or radiation. Vismodegib may have little effect on the treatment of BCC, given its high cost, the high cure rates achieved with standard therapies, and its unacceptable toxicity profile in patients with a non-life-threatening disease. However, vismodegib's novel mechanism of action, oral dosage form, preliminary efficacy, and tolerability compared with cytotoxic chemotherapy may make it an attractive candidate for the treatment of other cancers.