Alternative Vismodegib Dosing Regimen for Patients with Basal Cell Carcinoma

Basal cell carcinomas (BCCs) are the most common type of skin cancer. BCCs are unlikely to metastasize; however, locally advanced, metastatic, and refractory BCCs not amendable to surgery or radiation therapy can be destructive. 1 Systemic treatment with

various alternative long-term dosing regimens have been proposed; however, an optimal, tolerable dosing regimen to minimize both BCC burden and adverse effects is under debate.We propose an alternative dosing regimen to balance drug efficacy and tolerability.
A single-center retrospective case series was performed at the University of Alabama at Birmingham (UAB) and reported side effects, safety, and efficacy for an alternative vismodegib dosing pattern.The alternative dosing schedule consisted of vismodegib 150 mg daily for seven days followed by a 21-day drug holiday.This dosing pattern was prescribed to six patients all followed by a single provider.
The average patient age was 67 years old.Three patients were female with basal cell nevus syndrome (BCNS) and three patients were men, two with extensive BCCs and one with a BCC refractory to radiation and surgery.All six patients were initially started on vismodegib 150 mg daily until experiencing intolerable side effects (mean = 2.6 months).The most common adverse effects were muscle spasms (100%), dysgeusia (100%), alopecia (67%), fatigue (50%), and nausea (50%).All patients reported improvement or resolution of most adverse effects following the initiation of the alternative dosing pattern.Individual patients reported unchanged alopecia, fatigue and muscle spasms, however, these were not treatment limiting.Patients continued this alternative treatment regimen for an average of 30.7 months.In terms of BCC disease progression and recurrence, four patients achieved reduction in BCC size and remained free of any new BCC development and two patients developed new BCCs.One patient with BCNS developed a BCC of the left nasal tip 24 months into treatment and a second patient developed a BCC during a drug-holiday for radiation of squamous cell carcinoma of the lung.After he restarted vismodegib for seven days on followed by a 21-day drug holiday, however, this new BCC decreased in size and no additional BCCs were detected.(Table 1) Alternative vismodegib dosing regimens for patients with recurrent or unresectable BCCs has been reported to reduce intolerable adverse effects in patients requiring long term therapy. 3,4Dreno et al reported an alternative vismodegib dosing regimen of 150 mg daily for 12 weeks-on/24 weeks-off/12 weeks-on was more tolerable than a dosing regimen of 150 mg oral vismodegib x 24 weeks-on/24 weeks-off/8 weeks-on.Several other studies have compared an alternative vismodegib dosing schedule of 150 mg daily with weekend-off drug holidays.Overall, both alternative regimens report a decrease in adverse effects and patients saw either remission or a significant size reduction of existing BCCs. 3,4,5,6 individualized vismodegib maintenance dosing regimen is ideal for patients who require long-term therapy.Our alternative long-term dosing schedule of vismodegib 150 mg daily for seven days followed by a 21-day drug holiday may provide therapeutic effects without intolerable side effects.It's not clear what maintenance schedule of vismodegib is ideal for patients requiring long-term treatment; however, future prospective studies may elucidate a regimen that

DISCUSSION
minimizes both BCC burden and adverse effects.

Table 1 .
Patient demographics, indication for therapy, standard and alternative vismodegib treatment durations, adverse effects, and treatment efficacy.Takes occasional drug holidays when receiving radiation for squamous cell carcinoma of the lung *