Compassionate use of vismodegib and adjuvant radiotherapy in the treatment of multiple locally advanced and inoperable basal cell carcinomas and squamous cell carcinomas of the skin
Authors: Robert M. Gathings, Courtney S. Orscheln, William W. Huang
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Vismodegib is a small molecule inhibitor of SMO (smoothened), a transcription gene present in the hedgehog signaling molecule pathway and implicated in the proliferation of basal cell carcinomas (BCCs).1Sekulic A. Migden M.R. Oro A.E. Dirix L. Lewis K.D. Hainsworth J.D. et al.Efficacy and safety of vismodegib in advanced basal-cell carcinoma.N Engl J Med. 2012; 366: 2171-2179Crossref PubMed Scopus (1122) Google Scholar In January 2012, vismodegib was approved by the Food and Drug Administration for the treatment in adults with metastatic BCCs, for the treatment of locally advanced BCCs that recurred following surgery, and in patients who are not candidates for surgery and/or radiation. Vismodegib is an ineffective treatment for cutaneous squamous cell carcinomas (SCCs). The use of vismodegib for the treatment of BCCs with concurrent adjuvant radiotherapy for the treatment of SCCs has not been previously reported in the literature. We report a case of numerous BCCs and progressive SCCs, successfully treated with vismodegib and concurrent external beam radiation, respectively. An 81-year-old Caucasian man presented with multiple ulcerative and exophytic lesions on his face, trunk, and extremities that were concerning for locally invasive nonmelanoma skin cancers. The patient had similarly concerning but less extensive lesions 2 years earlier but declined treatment and was subsequently lost to follow-up. In the interim, because of progressive dementia, the Department of Social Services assigned him a guardian. On exam, the patient had evidence of numerous extensive tumors of the face, trunk, and extremities (Fig 1). Consults with dermatologic surgery and plastic surgery specialists deemed that it was not feasible to remove all the lesions or treat them with radiation given their extensive number and severity. Palliation and hospice were recommended. In follow-up, progressive ectropion of the bilateral eyelids with resultant exposure keratopathy developed, and the ulcerative lesions on the face, trunk, and extremities worsened (Fig 1). After discussion with the patient's guardian, the patient was started on vismodegib 150 mg daily oral therapy in August 2012. At the patient's 10-week follow-up, many of the tumors had almost completely resolved; however, lesions on the left parietal scalp, left zygoma, and left lower leg showed evidence of progression. Subsequent biopsies were consistent with invasive SCCs. The patient was referred to radiation oncology for possible radiotherapy. Over the next 7 weeks, the patient received 60 Gy (intensity modulated radiation therapy technique) and 40/48 Gy (en face electrons) to the left parietal scalp and left zygoma. At the patient's most recent follow-up in August 2013, most of the tumor burden from his BCCs had resolved or significantly thinned, leaving atrophic plaques (Fig 2). The SCC on the left zygoma had shrunken significantly enough to allow the patient to become a candidate for surgical repair of his ectropion (Fig 2). Our case illustrates that SCCs that emerge while on vismodegib for BCCs can be successfully and concurrently treated with external beam radiation. Standard doses for SCC were given over a 7-week timeframe with good response. This finding is particularly pertinent given the recently reported observation of SCC emergence after vismodegib treatment.2Chang A.L. Oro A.E. Initial assessment of tumor regrowth after vismodegib in advanced basal call carcinoma.Arch Dermatol. 2012; 148: 1324-1325Crossref PubMed Scopus (154) Google Scholar, 3Iarrobino A. Messina J.L. Kudchadkar R. Sondak V.K. Emergence of a squamous cell carcinoma phenotype following treatment of metastatic basal cell carcinoma with vismodegib.J Am Acad Dermatol. 2013; 69: e33-e34Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Further studies are needed to assess this potential complication of vismodegib therapy; however, for those patients on vismodegib who experience progressive locally invasive SCCs not amenable to surgical intervention, external beam radiation remains a viable treatment option.