Cidofovir for the treatment of recurrent respiratory papillomatosis: a review of the literature.
Recurrent respiratory papillomatosis (RRP) is a rare but potentially severe disease caused by papillomavirus, most often types 6 and 11. The disease, which occurs in both juvenile and adult forms, is characterized by benign epithelial tumors of the airway that most frequently affect the larynx but can also spread along the entire aerodigestive tract. Recurrent respiratory papillomatosis is the most common benign neoplasm of the larynx in children and the second most frequent cause of childhood hoarseness. Standard treatment, which is palliative only, consists of surgical excision of papillomata to maintain airway patency and improve voice quality. Recurrence despite repeated surgical procedures is the rule. To date, incorporation of adjuvant treatments has not been reliably beneficial in altering the disease course. Several case series have described promising results with cidofovir, a cytosine nucleoside analog with antiviral activity. To evaluate the data available on the safety and efficacy of cidofovir for the treatment of RRP, we conducted a MEDLINE search for all case reports or series from January 1966-August 2004 describing cidofovir therapy in either adults or children with RRP. The bibliographies of qualifying articles were also searched for relevant references. In both adults and children with mild-to-severe RRP, intralesional administration of cidofovir directly into the site of papillomata was associated with partial-to-complete regression of papillomata, improvement in voice quality and airway status, and decreased need for surgery. Wide variation in intralesional cidofovir dose (2-57 mg), frequency (every 2-8 wks), and duration (4 mo-4 yrs) was found. Successful outcomes have also been reported with intravenous cidofovir, but data are limited to three case reports. Rash, headache, and precordialgia were the only adverse effects reported with intralesional cidofovir. Nephrotoxicity and neutropenia secondary to either intralesional or intravenous cidofovir were not observed. Long-term risks associated with intralesional administration remain to be seen. Further studies are necessary to determine the most appropriate dose, frequency, and duration of therapy, and to fully characterize the safety profile profile of cidofovir when given intralesionally.
Shehab
Nadine
N
Department of Pharmacy Services, University of Michigan Health System, University Hospital, Ann Arbor, Michigan 48109-0008, USA. nshehab@umich.edu
Sweet
Burgunda V
BV
Hogikyan
Norman D
ND
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D000077404:Cidofovir; D002986:Clinical Trials as Topic; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000601:surgery; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000601:surgery; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010212:Papilloma / Q000188:drug therapy* / Q000601:surgery; D012142:Respiratory Tract Neoplasms / Q000188:drug therapy* / Q000601:surgery
D000970:Antineoplastic Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir