Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area

Abstract

Purpose Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Methods Retrospective chart review of six consecutive patients with biopsy-proven orbital basal cell carcinoma and two additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day). Results Basal cell carcinoma extended into the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (one with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neo-adjuvant or adjuvant therapies there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effect was muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Conclusions Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

“…The localization in target neurons is in line with the findings that Shh influences OSN axon growth and branching (11). Intriguingly, a low Shh level in human nasal mucus has been associated with reduced sense of smell (hyposmia) (8,9). In addition, distortion of smell perception (dysosmia) is a side effect of the anticancer drug and Smo inhibitor vismodegib (GDC0449, Erivedge) (9).…”

“…In light of the OR transport regulatory mechanism identified in flies, it is interesting to note that the most extensively studied mammalian Hh family member, Sonic hedgehog (Shh), is present in human nasal mucus as well as in dendrites of OSN target neurons in the rat olfactory bulb of the brain (8)(9)(10). The localization in target neurons is in line with the findings that Shh influences OSN axon growth and branching (11).…”

“…Interestingly, data that Shh indeed may regulate olfactory perception comes from clinical studies which have found a correlation between hyposmia and low Shh levels in nasal mucosa (8,28). Further evidence that the Hh pathway regulates olfactory perception in humans comes from the finding that dysosmia is a side effect of the anticancer drug, and Smo inhibitor, vismodegib (9). These observations also imply that Hh regulation of ciliary OR transport is evolutionarily conserved between the mouse and humans.…”

“…Intriguingly, a low Shh level in human nasal mucus has been associated with reduced sense of smell (hyposmia) (8,9). In addition, distortion of smell perception (dysosmia) is a side effect of the anticancer drug and Smo inhibitor vismodegib (GDC0449, Erivedge) (9). Taken together, these observations lead to the intriguing question of whether Hh-dependent regulation of OR availability and odorant responsiveness is evolutionary conserved to mammals.…”

Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome

“…To date, however, reports of Hedgehog pathway inhibition in patients with orbital or periocular lesions have been limited to single case reports or small case series. [7][8][9][17][18][19][20] There is room for reporting of additional experience in this particular patient population. We herein report our clinical experience with Hedgehog pathway inhibition in patients with locally advanced or metastatic orbital or periocular BCC and in patients with basal cell nevus syndrome and significant periocular lesions.…”