Safety and dosing of bevacizumab (Avastin) for the treatment of recurrent respiratory papillomatosis

Simon R Best, Aaron D. Friedman, Tali Landau-Zemer, Anca M. Barbu, James A. Burns, Mason W. Freeman, Yuan Di Halvorsen, Robert E. Hillman, Steven M. Zeitels

Research output: Contribution to journalArticle

Abstract

Objectives: 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 their participation in the initial clinical trial with a single-site lower dose (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.

Original languageEnglish (US)
Pages (from-to)587-593
Number of pages7
JournalAnnals of Otology, Rhinology and Laryngology
Volume121
Issue number9
StatePublished - Sep 2012
Externally publishedYes

Fingerprint

Safety
Injections
Therapeutics
Recurrent respiratory papillomatosis
Bevacizumab
Angiogenesis Inhibitors
Solid-State Lasers
Papilloma
United States Food and Drug Administration
Operating Rooms
Larynx
Clinical Trials
Wounds and Injuries
Serum
Pharmaceutical Preparations

Keywords

  • Avastin
  • Bevacizumab
  • Glottis
  • KTP laser
  • Larynx
  • Papilloma
  • Respiratory papillomatosis
  • Toxicity
  • Vocal cord
  • Voice

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Best, S. R., Friedman, A. D., Landau-Zemer, T., Barbu, A. M., Burns, J. A., Freeman, M. W., ... Zeitels, S. M. (2012). Safety and dosing of bevacizumab (Avastin) for the treatment of recurrent respiratory papillomatosis. Annals of Otology, Rhinology and Laryngology, 121(9), 587-593.

Safety and dosing of bevacizumab (Avastin) for the treatment of recurrent respiratory papillomatosis. / Best, Simon R; Friedman, Aaron D.; Landau-Zemer, Tali; Barbu, Anca M.; Burns, James A.; Freeman, Mason W.; Halvorsen, Yuan Di; Hillman, Robert E.; Zeitels, Steven M.

In: Annals of Otology, Rhinology and Laryngology, Vol. 121, No. 9, 09.2012, p. 587-593.

Research output: Contribution to journalArticle

Best, SR, Friedman, AD, Landau-Zemer, T, Barbu, AM, Burns, JA, Freeman, MW, Halvorsen, YD, Hillman, RE & Zeitels, SM 2012, 'Safety and dosing of bevacizumab (Avastin) for the treatment of recurrent respiratory papillomatosis', Annals of Otology, Rhinology and Laryngology, vol. 121, no. 9, pp. 587-593.
Best, Simon R ; Friedman, Aaron D. ; Landau-Zemer, Tali ; Barbu, Anca M. ; Burns, James A. ; Freeman, Mason W. ; Halvorsen, Yuan Di ; Hillman, Robert E. ; Zeitels, Steven M. / Safety and dosing of bevacizumab (Avastin) for the treatment of recurrent respiratory papillomatosis. In: Annals of Otology, Rhinology and Laryngology. 2012 ; Vol. 121, No. 9. pp. 587-593.
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AU - Burns, James A.

AU - Freeman, Mason W.

AU - Halvorsen, Yuan Di

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N2 - Objectives: 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 their participation in the initial clinical trial with a single-site lower dose (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.

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