gdc-0449 and Orbital-Neoplasms

Basal cell cancer is the most common cutaneous malignancy. It rarely presents with locally advanced or metastatic disease. Rare presentations such as intraorbital invasion remain a difficult clinical problem with significant potential morbidity. There is no review of sonic hedgehog pathway inhibitors (HPIs) for intraorbital basal cell cancer, and evidence regarding optimal management is limited.. To evaluate the evidence for the management of intraorbital basal cell cancer with HPIs.. A search to identify evidence for treatment intraorbital basal cell cancers with HPIs to date was performed in PubMed database and OVID using the phrases "basal cell cancer/carcinoma/BCC," "intraorbital," "orbital," "ocular," "periocular," "vismodegib," "GDC-0449," "sonidegib," and "LDE224," in various combinations with Boolean operators "AND" and "OR.". Rigorous clinical trials have previously reported the use of vismodegib and sonidegib in locally advanced and metastatic basal cell carcinoma (BCC). However, specific descriptions of treatment of intraorbital tumors are rarely presented in detail adequate for analysis. Twenty-two cases of intraorbital BCC treated with vismodegib have been described in the literature, and no cases using sonidegib were identified. These vary in quality, but highlight important questions regarding optimal treatment duration, follow-up, and adjunctive therapies. Reports describing locally advanced BCC in various facial and periocular locations, but without specific mention of intraorbital invasion, were excluded.. Vismodegib is an attractive eye and vision-sparing option in patients with locally advanced intraorbital basal cell cancer whose other options often include exenteration, radiation, or other radical surgery.

Topics: Administration, Oral; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Hedgehog Proteins; Humans; Lacrimal Apparatus; Male; Middle Aged; Neoplasm Recurrence, Local; Orbital Neoplasms; Pyridines; Salvage Therapy; Skin Neoplasms

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: Administration, Oral; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Female; Humans; Male; Orbital Neoplasms; Pyridines; Skin Neoplasms; Treatment Outcome

Topics: Aged; Anilides; Antineoplastic Agents; Basal Cell Nevus Syndrome; Ear Neoplasms; Female; Humans; Male; Middle Aged; Orbital Neoplasms; Pyridines

Topics: Administration, Oral; Aged; Anilides; Antineoplastic Agents; Biopsy; Carcinoma, Basal Cell; Chemotherapy, Adjuvant; Hedgehog Proteins; Humans; Magnetic Resonance Imaging; Male; Ophthalmologic Surgical Procedures; Orbital Neoplasms; Pyridines

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