TREATMENT OF SEVERE LARYNGEAL PAPILLOMATOSIS WITH INTRALESIONAL INJECTIONS OF CIDOFOVIR S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPY)CYTOSINE]

Respiratory papillomatosis is a rare and often severe disease, usually localized in the larynx. It may cause respiratory distress and even l ife-threatening obstruction of the airways. Treatment is generally bas ed on the evaporation of the lesions with a CO2 laser, but microsurger y, cytotoxic and/or cytostatic drugs, interferons, and vaccines are al so used. Cidofovir )-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] (HPMPC) was shown to suppress the growth of tumors induced by rabbit p apillomavirus as well as human papillomavirus (HPV). The efficacy of c idofovir was assessed in 17 patients with severe respiratory papilloma tosis. Cidofovir at a concentration of 2.5 mg/ml was injected directly in the different laryngeal papillomatous lesions during microlaryngos copy under general anesthesia. Biopsies were taken before the treatmen t was started both for anatomopathology and viral typing. HPMPC kineti cs in serum was monitored in three patients, the drug levels being det ermined by high-performance liquid chromatography. Complete disappeara nce of the papillomatosis was observed in 14 patients. Four patients r elapsed and were successfully treated again with cidofovir. Of the thr ee remaining patients, one progressed while under treatment with cidof ovir, after an initial marked response. One patient had a partial remi ssion and remained stable for more than 1 year after the last injectio n. 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 papillo matosis is a powerful new therapeutic approach for this disease. Treat ment was well tolerated, and no significant side effects were noted. ( C) 1998 Wiley-Liss, Inc.