gdc-0449 and Eyelid-Neoplasms

Locally-advanced periocular basal cell carcinoma (BCC) pose many therapeutic challenges due to the need to preserve functionality and cosmesis of the orbit and periocular area. Surgical excision and subsequent orbital exenteration are two recognized modalities of treatment. Vismodegib is currently an FDA-approved monotherapy for locally-advanced and metastatic BCC. We present a case of the use of vismodegib as neoadjuvant therapy prior to surgical excision of a locally-advanced periocular recurrent BCC in a 75-year-old male. The patient’s tumor successfully responded to vismodegib allowing surgical excision with clear margins. The orbit was saved in a patient who otherwise would have required complete orbital exenteration. J Drugs Dermatol. 20(5):552-554. doi:10.36849/JDD.5661.

Topics: Administration, Oral; Aged; Anilides; Carcinoma, Basal Cell; Eyelid Neoplasms; Eyelids; Humans; Magnetic Resonance Imaging; Male; Margins of Excision; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Organ Sparing Treatments; Pyridines; Skin Neoplasms; Treatment Outcome

Topics: Aged; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Chemical and Drug Induced Liver Injury; Eyelid Neoplasms; Humans; Male; Pyridines; Skin Neoplasms

Topics: Aged, 80 and over; Anilides; Carcinoma, Basal Cell; Eyelid Neoplasms; Humans; Male; Neoadjuvant Therapy; Pyridines

Locally advanced (T4 per American Joint Committee on Cancer (AJCC) 8th edition) periocular basal cell carcinoma (BCC) can lead to loss of the eye. We report the neoadjuvant use of vismodegib followed by surgery in patients with such lesions with eye preservation as primary goal.. This retrospective interventional study includes all patients with a T4 periocular BCC (per 8th edition AJCC for eyelid carcinoma) treated by the senior author between 2013 and 2017 with neoadjuvant vismodegib prior to definitive surgery.. Eight patients had a T4 tumour. Six patients presented with recurrent disease. Indications for neoadjuvant treatment were an unresectable tumour in one patient, an attempt to avoid an orbital exenteration in six patients and an attempt to avoid disfiguring facial surgery in one patient. Patients were treated for a median of 14 months (range: 4-36 months). All patients underwent an eye-sparing surgery following neoadjuvant vismodegib and all final surgical margins were negative for tumour. Five patients had a complete response to vismodegib with no microscopic residual BCC found during surgery; three patients had a significant partial response with residual tumour found on pathology. At last follow-up, a mean of 18 (range: 6-43) months after surgery, all patients were off-vismodegib and alive without evidence of disease.. Neoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was well tolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anilides; Biopsy; Carcinoma, Basal Cell; Dose-Response Relationship, Drug; Eyelid Neoplasms; Eyelids; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Ophthalmologic Surgical Procedures; Pyridines; Retrospective Studies; Treatment Outcome

To evaluate the effectiveness of vismodegib, a Hedgehog pathway inhibitor, in treating orbital and advanced periocular basal cell carcinoma (BCC) in Israeli multidisciplinary medical centers.. Retrospective case series.. Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbital or periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers.. The cohort included 21 patients (16 male) of median age 76 years with periocular (n=6) or orbital (n=15) BCC. Median duration of treatment was 9 months, with follow-up of 26 months (range 9-60 months) overall and 17 months after treatment cessation. Clinical response was complete in 10 patients, partial in 10 patients, and stable in 1 patient. Among the complete responders, 5 maintained a complete response at 16 months, and 3 who stopped treatment had a recurrence 8 months later. Almost all treatment-related adverse reactions were graded 1 or 2 (low-grade). The most common grade 1 or 2 complications were muscle spasm (76%), followed by dysgeusia (57%), alopecia (47%), weight loss (47%) and decreased appetite (19%). The only grade 3 or 4 adverse event was hepatotoxicity (10%). Eight patients discontinued treatment because of side effects. Five patients died, most from reasons unrelated to vismodegib therapy, except for 1 patient who died from possibly treatment-related sepsis (grade 5 adverse event).. To our knowledge, this is the only study generated outside the United States and Europe, and it represents the largest study to date on vismodegib therapy for locally advanced periocular BCC. Treatment according to an individualized maximally tolerated dose may achieve a comparable response to the ERIVANCE protocol. Longer-term studies are needed to assess prognosis.

Topics: Aged; Aged, 80 and over; Anilides; Carcinoma, Basal Cell; Eyelid Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Orbital Neoplasms; Pyridines; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Adult; Anilides; Antineoplastic Agents; Basal Cell Nevus Syndrome; Eyelid Neoplasms; Hedgehog Proteins; Humans; Magnetic Resonance Imaging; Male; Maxillary Sinus Neoplasms; Neoplasms, Multiple Primary; Pyridines; Skin Neoplasms; Tomography, X-Ray Computed

Basal cell carcinoma (BCC) represents 90% of malignant eyelid tumors and is locally invasive and destructive, if left untreated.. To assess the feasibility of using vismodegib for periocular and orbital BCC based on its efficacy and tolerability.. In this prospective observational case series, consecutive patients with periocular or orbital BCC who met criteria for treatment with vismodegib were recruited prospectively during an 8-month period from February through September 2012 from 2 academic hospitals. Seven patients received oral vismodegib, 150 mg daily, until maximum clinical response was achieved, the tumor progressed, or the patient could no longer tolerate adverse effects. Clinical response and adverse effects related to treatment were recorded. The primary endpoint was reduction in lesion size, measured as percentage change in the externally visible dimension.. Oral vismodegib.. All 7 patients had locally advanced, biopsy-proven, infiltrative BCC that was not amenable to surgical resection or radiation. No patients had metastatic disease at presentation. The mean patient age was 71 years (range, 43-100 years), and 4 patients (57%) had secondary orbital involvement. The mean lesion size was 3.4 cm (range, 1.0-6.0 cm), and all 7 cases (100%) represented recurrent tumors excised previously with controlled margins by frozen section or Mohs micrographic surgery. The mean treatment duration was 11 weeks (range, 4-16 weeks), and the mean duration of follow-up was 7.3 months (range, 5-10 months). Two patients (29%) demonstrated complete clinical regression, 2 (29%) demonstrated greater than 80% partial clinical regression, 2 (29%) demonstrated less than 35% partial clinical regression, and 1 (14%) progressed. Adverse reactions occurred in 6 patients (86%) and included alopecia (29%), dysgeusia (29%), muscle cramps (29%), and anorexia (14%). Two patients (29%) developed new squamous cell carcinomas (well-differentiated, keratoacanthoma type) at uninvolved sites including the eyebrow and forearm.. Vismodegib seems to be well-tolerated and effective for treating periocular and orbital BCC in about half of all cases. Patients receiving treatment should be monitored for new squamous cell carcinomas at uninvolved sites.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Eyelid Neoplasms; Female; Follow-Up Studies; Hedgehog Proteins; Humans; Male; Middle Aged; Orbital Neoplasms; Pilot Projects; Prospective Studies; Pyridines; Skin Neoplasms; Treatment Outcome