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

Abstract

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.

Estudo do efeito do Cidofovir na papilomatose laríngea recorrente em crianças: relato preliminar

“…They also recommended previous debulking. Snoeck 16 and Willian 22 , on the other hand, presented different methodologies: they performed local application of Cidofovir without any debulking (lesion removal). Snoeck, who was a pioneer in the use of Cidofovir for RLP, recommended a concentration of 2.5mg/ml and applied the medication until the lesions disappeared, but he only studied the adult population.…”

“…These patients needed more than one 3-application cycle to achieve good control of recurrences. However, these children did not have any type of changes in their laboratorial exams, clinical pathology analysis and also did not show any local or systemic side effect, as in accordance to other cases in the literature 15,16,20,21,26 . The only study described in the literature that reports side effects with local use of Cidofovir was published by Bienvenu 27 in 2002.…”

“…Cidofovir [(S)-1-(3-Hydroxy-2-Phosphonyimethoxypropyl) Cytosine, HPMPC, Vistide ® ] is an antiviral that has been proven quite effective in the inhibition of virus replication such as herpes, adenovirus, cytomegalovirus and papillomavirus [14][15][16] . This drug has been approved by the FDA (Food and Drug Administration) to be used in retinitis caused by cytomegalovirus in patients with AIDS.…”

“…They used a gel formulation in three patients with good outcomes. Its use in RLP was first reported by Snoeck in 1998 16 . Since then, several authors have been showing positive outcomes with the use of this medication in RLP treatments.…”

Successful treatment of severe respiratory papillomatosis with intravenous cidofovir and interferon α-2b

“…Benign epithelial proliferations may result in obstructions of the airways leading to chronic changes of the respiratory tract [1,2]. Treatment is generally based on surgical ablation of the lesions, usually using a carbon dioxide laser [2].…”