title: Local injection of bevacizumab (Avastin) and angiolytic KTP laser treatment of recurrent respiratory papillomatosis of the vocal folds: a prospective study.
abstract: OBJECTIVE
  Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a pegative impact on the voice and whether there were local or systemic complications.
  
  
  METHODS
  A prospective open-label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained.
  
  
  RESULTS
  All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range.
  
  
  CONCLUSIONS
  This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary.
authors.affiliation: Department of Surgery, Harvard Medical School, and the Center for Laryngeal Surgery and Voice Rehabilitation the Massachusetts General Hospital Institute of Health Professions, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Zeitels
authors.forename: Anca M
authors.initials: AM
authors.lastname: Barbu
authors.forename: Tali
authors.initials: T
authors.lastname: Landau-Zemer
authors.forename: Gerardo
authors.initials: G
authors.lastname: Lopez-Guerra
authors.forename: James A
authors.initials: JA
authors.lastname: Burns
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Friedman
authors.forename: Mason W
authors.initials: MW
authors.lastname: Freeman
authors.forename: Yuan-Di
authors.initials: YD
authors.lastname: Halvorsen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hillman
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D007267:Injections; D007818:Laryngeal Diseases / Q000628:therapy*; D053844:Lasers, Solid-State / Q000627:therapeutic use*; D008297:Male; D010212:Papilloma / Q000628:therapy*; D010699:Phonation / Q000502:physiology; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome; D014827:Vocal Cords
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab