title: An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma.
abstract: BACKGROUND
  Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.
  
  
  OBJECTIVE
  We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.
  
  
  METHODS
  This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.
  
  
  RESULTS
  Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4±2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.
  
  
  CONCLUSIONS
  Short follow-up time and no placebo control are limitations.
  
  
  CONCLUSIONS
  Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Mina Sarah
authors.initials: MS
authors.lastname: Ally
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Sumaira
authors.initials: S
authors.lastname: Aasi
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California; Scripps Clinic, Dermatologic Surgery Division, La Jolla, California.
authors.forename: Ashley
authors.initials: A
authors.lastname: Wysong
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Claudia
authors.initials: C
authors.lastname: Teng
authors.affiliation: School of Medicine, Stanford University, Stanford, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Anderson
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Irene
authors.initials: I
authors.lastname: Bailey-Healy
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Anthony
authors.initials: A
authors.lastname: Oro
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California; Department of Pathology, Stanford University, Stanford, California.
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California.
authors.forename: Anne Lynn
authors.initials: AL
authors.lastname: Chang
authors.affiliation: Department of Dermatology, Stanford University, Stanford, California. Electronic address: tangy@stanford.edu.
authors.forename: Jean Yuh
authors.initials: JY
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004408:Dysgeusia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015580:Mohs Surgery / Q000009:adverse effects*; D009120:Muscle Cramp / Q000139:chemically induced; D020360:Neoadjuvant Therapy; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D047368:Tumor Burden
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines
keywords: Mohs; basal cell carcinoma; neoadjuvant; surgery; surgical defect; vismodegib