Severe Respiratory Papillomatosis Research Articles

1133P - Systemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center

BackgroundRecurrent Respiratory papillomatosis (RRP) can result in significant morbidity due to effects on voice and breathing and often requires frequent debulking procedures, which can disrupt quality of life. Responses to current surgical and medical treatments are inconsistent and there are no systemic treatments proven to be consistently effective in managing this disease. Bevacizumab, an anti-angiogenic agent that targets the vascular endothelial growth factor (VEGF) has been used as systemic agent for the treatment of RRP. We present a retrospective analysis of safety, efficacy and clinical outcomes in thirteen patients who were treated with systemic bevacizumab. MethodsWe present a retrospective analysis of patients with severe RRP who received 10mg/kg or 15mg/kg systemic bevacizumab at 3 weekly intervals at a single academic tertiary care center. They were monitored for toxicity and response to treatment as measured by need for further surgical interventions and improvement of symptoms. ResultsTwelve patients received at least 2 doses of systemic bevacizumab for an average of 5 cycles. Overall the treatment was well tolerated with minimal side effects. The most common side effect was hypertension, which was experienced by 4 out of 12 patients. Two patients discontinued treatment due to side effects. One experienced grade 3 epistaxis and another patient developed hypertension and thrombocytopenia. Two other individuals tolerated treatment well however, therapy was suspended due to insurance denial. All patients reported an improvement in symptoms including, improved quality of voice and breathing as well as decreased cough. The average number of surgical interventions in the year prior to administration of systemic bevacizumab was 4, with most individuals requiring intervention at a frequency of 2-4 months. Following treatment, only 4 of the 12 patients required one surgical intervention. ConclusionsSystemic bevacizumab appears to be a safe and well tolerated treatment option for patients with severe RRP. It demonstrates promising efficacy on symptoms including voice quality and improved breathing as well as decreased requirement for surgical therapy. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Long-term follow-up of pediatric recurrent respiratory papillomatosis managed with intralesional cidofovir.

Cidofovir is an acyclic nucleotide phosphonate antiviral medication that has been used intralesionally for the treatment of severe respiratory papillomatosis (RRP) in pediatric patients. The long-term efficacy of this medication was assessed in 11 children with severe RRP who previously required operative debulking every 2 to 6 weeks to maintain airway patency. Clinical case series. Ten of these children have completed therapy. Five are disease free over a mean follow-up period of 51.6 months. Five other patients with active RRP decreased their mean severity scores from 17.8 (range 11-26) to 4.0 (range 2-6) and no longer require cidofovir. One patient continues to receive cidofovir for recurrent disease after an initial favorable response. Throughout the 6-year observational period, no patients demonstrated any adverse effects, laboratory abnormalities, or evidence of carcinogenesis. Intralesional cidofovir is a useful adjunct for managing children with tenuous airways caused by previously uncontrolled papilloma.

Intralesional Cidofovir for Recurrent Respiratory Papillomatosis in Children

PRANSKY, SETH M.; MAGIT, ANTHONY E.; KEARNS, DONALD B.; KANG, RICHARD D.; DUNCAN, NEWTON O. Author Information

Intralesional cidofovir for recurrent respiratory papillomatosis in children.

To assess the potential benefit of intralesional administration of cidofovir, an acyclic nucleoside phosphonate with activity against several DNA viruses, for treating severe respiratory papillomas in pediatric patients. Prospective case series. Tertiary care children's hospitals. Five pediatric patients with severe recurrent respiratory papillomatosis requiring laryngoscopy with carbon dioxide laser therapy more frequently than once a month to maintain airway patency. Each patient underwent between 12 and 33 laryngoscopies with laser treatment prior to being injected with cidofovir. Microsuspension laryngoscopy with intralesional injection of cidofovir (Vistide) in conjunction with mechanical debulking and carbon dioxide laser of papillomas. Papilloma stage at time of serial laryngoscopies. One patient was disease free and 3 patients demonstrated a dramatic response to adjuvant therapy with cidofovir at the 9-month follow-up visit after the last injection of cidofovir. One patient showed an improvement in papilloma stage that was possibly related to concurrent therapy with interferon. Intralesional injection of cidofovir seems to be of benefit in the treatment of severe respiratory papillomatosis in pediatric patients. Larger prospective studies with longer follow-up will be required before cidofovir can be considered an accepted means of managing this difficult disease.

Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine

Respiratory papillomatosis is a rare and often severe disease, usually localized in the larynx. It may cause respiratory distress and even life-threatening obstruction of the airways. Treatment is generally based on the evaporation of the lesions with a CO2 laser, but microsurgery, cytotoxic and/or cytostatic drugs, interferons, and vaccines are also used. Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC) was shown to suppress the growth of tumors induced by rabbit papillomavirus as well as human papillomavirus (HPV). The efficacy of cidofovir was assessed in 17 patients with severe respiratory papillomatosis. Cidofovir at a concentration of 2.5 mg/ml was injected directly in the different laryngeal papillomatous lesions during microlaryngoscopy under general anesthesia. Biopsies were taken before the treatment was started both for anatomopathology and viral typing. HPMPC kinetics in serum was monitored in three patients, the drug levels being determined by high-performance liquid chromatography. Complete disappearance of the papillomatosis was observed in 14 patients. Four patients relapsed and were successfully treated again with cidofovir. Of the three remaining patients, one progressed while under treatment with cidofovir, after an initial marked response. One patient had a partial remission and remained stable for more than 1 year after the last injection. He had a very aggressive and extensive disease originally. Finally, one patient was lost to follow-up after four injections. Intratumoral injections of cidofovir for the treatment of severe laryngeal papillomatosis is a powerful new therapeutic approach for this disease. Treatment was well tolerated, and no significant side effects were noted.