title: Safety and dosing of bevacizumab (avastin) for the treatment of recurrent respiratory papillomatosis.
abstract: OBJECTIVE
  Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP.
  
  
  METHODS
  Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after t heir participation in th e initial clinical trial with a single-site lowerdose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications.
  
  
  RESULTS
  One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx.
  
  
  CONCLUSIONS
  This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future.
authors.affiliation: Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Best
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Friedman
authors.forename: Tali
authors.initials: T
authors.lastname: Landau-Zemer
authors.forename: Anca M
authors.initials: AM
authors.lastname: Barbu
authors.forename: James A
authors.initials: JA
authors.lastname: Burns
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
authors.forename: Steven M
authors.initials: SM
authors.lastname: Zeitels
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053844:Lasers, Solid-State / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000601:surgery; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000601:surgery
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab