Systemic Use of Bevacizumab for Recurrent Respiratory Papillomatosis: Who, What, Where, When, and Why?

by Craig S. Derkay, MD, Emily E. Wikner, MD, Seth Pransky, MD, Simon R. Best, MD, Karen Zur, MD, Douglas R. Sidell, MD, Adam Klein, MD, Clark Rosen, MD, Frederick G. Dikkers, MD, and Romaine Johnson, MD •

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BACKGROUND

Recurrent respiratory papillomatosis (RRP) is a potentially lethal disease caused by the human papillomavirus (HPV) and characterized by recurrent papillomas in the aerodigestive tract. Cases of RRP are expected to be significantly reduced with increased acceptance of the HPV-9 vaccine. Currently, the mainstay of RRP treatment is surgical intervention, with a minority of patients requiring adjuvant medical therapies during their disease. Several adjuvant therapies have been administered, with little consensus on optimal timing of administration and which treatments are most effective. In the past, systemic interferon-α was used for severe RRP, and evidence showed it could prolong surgical intervals. However, the use of interferon-α for juvenile- onset RRP treatment has been curtailed due to serious side effects, including neurologic disorders, leukopenia, and thrombocytopenia. Thus far, systemic bevacizumab has a superior safety profile, with hypertension, epistaxis, proteinuria, and impaired wound healing the most common side effects reported. To achieve a lasting remission with a serviceable voice and patent airway, providers must consider how and when to approach intervention with adjuvants to limit the risks and damage from frequent airway surgeries. Bevacizumab is a monoclonal antibody that binds to and inhibits vascular endothelial growth factor expressed on papilloma epithelium. Preliminary results from intravenous bevacizumab, initiated for “salvage” and then continued as a maintenance medical treatment in patients with severe laryngeal, tracheal, and pulmonary RRP, have demonstrated dramatic clinical responses. The question arises of whether to embark on a paradigm shift from traditional repeated surgical treatments to early initiation of medical management utilizing bevacizumab as a primary treatment modality.

BEST PRACTICE

Administration of systemic bevacizumab earlier in the RRP disease process may provide the benefit of decreased disease progression in addition to minimizing surgical sequelae. Although additional controlled studies are needed to confirm these findings, a paradigm shift toward medical management of this vexing disease should be considered.