Intermittent Vismodegib Proposed For Advanced BCC

An intermittent vismodegib dosing schedule could be effective and well tolerated in advanced basal cell carcinoma

medwireNews: Intermittent dosing of the hedgehog signalling pathway inhibitor vismodegib may be feasible in advanced basal cell carcinoma (BCC) patients who are unable to tolerate a standard dosing regimen, researchers suggest.

The authors of a letter to JAMA Dermatology describe the outcome of seven patients who were given vismodegib in cycles of 1 week of treatment followed by 1–3 weeks off treatment, depending on adverse events (AEs).

They believe the intermittent schedule could be an alternative to offering multiple month-long treatment holidays in patients who do not tolerate treatment.

“This dosing schedule was well tolerated, and AEs were mild or resolved with less medication, as no patients discontinued vismodegib owing to treatment-related AEs”, say Peter Lee and co-authors, from the University of Minnesota in Minneapolis, USA.

Three patients achieved complete tumour resolution over 9–24 months of follow-up, including a patient with multiple facial BCCs who received 6 cycles on a 1 week on/1 week off basis, seven cycles on a 1 week on/2 weeks off, and 14 cycles on a 1 week on/3 weeks off basis.

A second patient achieved resolution of multiple recurrent and aggressive facial BCCs with eight cycles of 1 week on/1 week off, followed by 1 cycle on a 1 week on/2 weeks off basis and nine cycles of 1 week on/3 weeks off. The third patient had resolution of an incompletely resected periorbital BCC after five cycles of vismodegib on a 1 week on/ 3 weeks off basis.

The remaining four patients experienced an improvement, defined as a decrease in the size or number of BCCs.

One patient discontinued vismodegib and underwent Mohs micrographic surgery after a large BCC on their nose shrank; a patient with over 50 BCCs and another with basal cell nevus syndrome achieved a reduction in both the number and size of lesions; and the fourth patient experienced a decrease in their large periorbital BCC.

Most patients reported adverse events during treatment, with six of the seven experiencing mild fatigue and four dysgeusia. Arthralgia or arthritis were reported by three patients, as was muscle spasm, while two described Alopecia, and diarrhoea and constipation were each reported by one patient.

Treatment was reduced to a frequency of 1 week on/3 weeks off in patients with persistent side effects but none ended treatment because of AEs.

Noting a report of vismodegib therapy discontinuation in 17% of trial participants because of AEs, the researchers recommend: “An intermittent dosing schedule of vismodegib should be considered when treatment-related AEs would cause discontinuation of treatment.”

Nevertheless, acknowledging the limitations of their small, retrospective study, they conclude: “Pharmacokinetic and prospective randomized clinical trials are needed to determine the ideal intermittent regimen without causing resistance.”

Reference

Becker LR, Aakhus AE, Reich HC, Lee PK. A novel alternate dosing of vismodegib for treatment of patients with advanced basal cell carcinomas. JAMA Dermatol; Advance online publication 18 January 2017. doi:10.1001/jamadermatol.2016.5058

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