and dysgeusia than the continuous regimen. Similarly, the muscle cramps and dysgeusia in the present patients resolved within 1 month after interrupting the vismodegib regimen. Although pharmacokinetic studies have shown suboptimal efficacy and similar incidence and severity of adverse effects when vismodegib, 150 mg, was used once weekly or 3 times weekly, no studies to our knowledge have investigated the efficacy of continuous daily doses with drug breaks in between. 3 We found a mean of 1.4 new surgically eligible BCCs per year per patient undergoing intermittent therapy, which is comparable to the 2.0 new surgically eligible BCCs per year per patient found by Tang et al 1 in patients undergoing a standard continuous daily regimen. Vismodegib resistance occurs in patients who undergo continuous vismodegib dosing. 4 The frequency of resistance in patients who undergo an intermittent form of treatment is largely unknown. Combination therapy with hedgehog pathway inhibitors downstream of smoothened, such as itraconazole and arsenic trioxide, provide opportunities to increase efficacy and possibly reduce the incidence of resistance. 5,6 Conclusions | Overall, our clinical experience suggests that intermittent therapy is an effective way to overcome problems with adverse effects and compliance with vismodegib treatment of BCNS. Photographic and histologic documentations of tumors and randomized clinical trials are warranted to quantify the ideal duration of the intermittent regimen and compare the addition of combination therapies to overcome potential drug resistance.

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