Systemic bevacizumab for recurrent respiratory papillomatosis: A national survey

Abstract

Objective Aggressive laryngeal, tracheal and pulmonary papilloma is an extremely challenging clinical problem without proven treatment options. A recent German report documented promising results with systemic bevacizumab. The objective of this study is to report the initial experience of this novel treatment in the United States for Recurrent Respiratory Papillomatosis (RRP). Study Design Cases series Methods Electronic survey of the RRP Task Force of the American Society of Pediatric Otolaryngology, American Broncho-Esophagological Association, and physicians known to the authors to have used systemic bevacizumab for RRP. Results Eleven completed surveys were obtained. In three cases, systemic bevacizumab was considered clinically but not administered. Eight patients were treated with systemic bevacizumab, all for aggressive papillomatosis uncontrolled by surgical and adjuvant therapy, including 7 of 8 with pulmonary disease. Treatment dosing ranged from 5–10 mg/kg every 2–4 weeks, with all patients responding (7/8 partial response, 1/8 complete response). In four patients who had post-bevacizumab chest imaging, three demonstrated improvement of disease and one stabilization. Treatment interval could be lengthened in seven patients and clinical response maintained. One patient with long-standing pulmonary disease (>10 years) was diagnosed with malignant transformation while on treatment and bevacizumab was discontinued in lieu of other chemotherapeutic agents. All other patients continue on systemic bevacizumab with minimal complications (hemoptysis n=1; proteinuria n=1). Conclusions Systemic bevacizumab appears to have significant promise in the most treatment-resistant and aggressive forms of papillomatosis with a low complication profile. These results suggest bevacizumab should be studied in a formal clinical trial for RRP.

Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children

“…Only three reports on the use of systemic bevacizumab in children have been published (Table I). The authors observed satisfactory results, with a reduction in the need for surgery, improvement of quality of life, 6,7,9 with no severe toxicity. However, it is important to note that all of the studies were small, with limited treatment duration and short follow-up.…”

“…Bevacizumab has no effect on the viral DNA and mechanisms of apoptosis, but presents a direct antiangiogenic action that affects tumor growth 9 and is responsible for the therapeutic effect. 9 It is responsible for reduction of the lesions' size and the improvement of airway permeability, without eradicating the viral infection and risk of recurrence after suspending the treatment. On the first patient, we used a 10-mg/kg dosing schedule, which is recommended for adults in most case reports published in the literature.…”

Pharyngeal Papilloma: a Rare Non-Pulmonary Cause of Hemoptysis

“…Another promising adjuvant pharmacological agent is bevacizumab -a recombinant monoclonal humanized antibody -that blocks angiogenesis by inhibiting the human vascular endothelial growth factor A (VEGF-A), which has been shown to play an important role in the pathogenesis of RRP (14). Several recent studies have demonstrated its satisfactory results by decreasing the growth of papillomatous lesions and prolonging intervals between the surgical procedures (15,16).…”

Rezidivierende respiratorische Papillomatose: Aktuelles zu Diagnose und Therapie

“…Auch im In-vitro-Versuch zeigt sich eine erhöhte Kanzerogenität des Medikaments, sodass die Therapie trotz vielversprechender Ansprechraten kontrovers diskutiert wird [42]. Erste klinische Arbeiten zu dieser Therapie zeigen vielversprechende Ansprechraten mit Verlängerung der Therapieintervalle und partiellen sowie zum Teil auch kompletten Remissionen [43,44]. Der Antikörper wird sowohl lokal injiziert als auch bei schweren Verläufen systemisch verabreicht.…”