In the January 2023 issue of Laryngoscope, renowned authors led by Craig S. Derkay present a comprehensive overview of a promising medical intervention for Recurrent Respiratory Papillomatosis (RRP). This disease, rooted in the human papillomavirus (HPV), has primarily been treated through surgical means. However, with advancements in medical research and therapeutics, bevacizumab, a monoclonal antibody, has emerged as a potential game-changer. Derkay and his team delve deep into the systemic use of this antibody, questioning the traditional surgical approach and shedding light on the possibilities and challenges associated with this new treatment. Through this Triological Society Best Practice Paper, readers are invited to understand the specifics – the ‘Who, What, Where, When, and Why’ – of using bevacizumab for managing RRP, a shift that might herald a new era in its treatment paradigm.
Background: Recurrent respiratory papillomatosis (RRP) is a severe disease resulting from the human papillomavirus (HPV). It leads to repeated papilloma growth in the aerodigestive tract. While the HPV-9 vaccine promises to reduce RRP cases, surgery remains the dominant treatment approach. Some patients, however, also require additional medical therapies. Previously, Interferon-α was a treatment option, but due to significant side effects, it’s less favored today. Systemic bevacizumab has emerged as a safer alternative.
Role of Bevacizumab (Avastin®): Bevacizumab, a monoclonal antibody, inhibits vascular endothelial growth factor (VEGF) found on papilloma epithelium. Preliminary results have showcased its potential in treating severe laryngeal, tracheal, and pulmonary RRP. This raises the question: should RRP be approached more from a medical management perspective using bevacizumab rather than primarily relying on surgical interventions?
Literature Review: Studies have indicated that RRP tissues exhibit higher VEGF levels than normal laryngeal tissues. Bevacizumab’s ability to bind to VEGF inhibits angiogenesis, which in turn restricts papilloma growth. Notably, systemic bevacizumab treatments have demonstrated remarkable success in RRP cases, especially among patients who did not respond well to frequent surgical interventions or other adjuvant therapies. In many instances, surgeries were no longer required post bevacizumab treatment.
The successes with systemic bevacizumab have led to a rethinking of RRP management. Instead of multiple surgeries, which could lead to scarring and long-term voice issues, there’s a push towards a non-surgical approach to limit the disease’s spread to the trachea and lungs. Additionally, the emotional and financial toll, potential health risks, and the societal impact of recurring surgeries are other factors favouring this shift.
However, reservations exist. The long-term effects of bevacizumab remain uncertain, especially in juvenile-onset RRP cases. Disease recurrence after halting treatment has been observed, and the definitive treatment endpoint remains ambiguous.
Dosing and Treatment Protocols: Standardized dosing protocols are not yet universally accepted. However, some recommended practices include initiating treatment with intravenous infusions at 10 mg/kg concentration and adjusting based on disease response and individual patient conditions. For optimal results, medical colleagues familiar with bevacizumab should be engaged, and the treatment should be conducted in a multidisciplinary infusion centre.
Conclusion: While bevacizumab presents a promising shift in RRP management, its long-term effects and ideal dosing protocols need further research. Collaboration among specialists and the use of well-equipped centers can maximize patient outcomes and minimize complications. Some centers have already begun using intravenous bevacizumab as a primary treatment in paediatric cases, indicating a possible future direction for RRP management.
References / The Compete paper can accessed at the following link:
Derkay CS, Wikner EE, Pransky S, Best SR, Zur K, Sidell DR, Klein A, Rosen C, Dikkers FG, Johnson R. Systemic Use of Bevacizumab for Recurrent Respiratory Papillomatosis: Who, What, Where, When, and Why? Laryngoscope. 2023 Jan;133(1):2-3. doi: 10.1002/lary.30180. Epub 2022 May 11: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10084367/pdf/LARY-133-2.pdf
Prof. Dr. Prahlada N. B
8 November 2023