Cidofovir for the Treatment of Recurrent Respiratory Papillomatosis

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPPONI, A; GONZALEZ, L

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Recurrent Respiratory Papillomatosis (RRP) is a disease caused by the Human Papilloma Virus (HPV) characterized by the presence of airway epithelial tumors. The most commonly affected area is the larynx. Its manifestations vary from dysphonia to total airway obstruction. Treatment consists in surgical resection of the papilloma to keep the airway patent and to improve the voice quality. It presents a widely variable and unpredictable evolution, in some cases with a high rate of recurrence. So far, multiple adjuvant therapies have been tried in order to decrease the number of procedures or to prolong the interval between them. The intralesional use of cidofovir is proposed as adjuvant therapy for the treatment of RRP.TechnologyCidofovir is a cytidine analogue that suppresses viral replication by selectively inhibiting the polymerase DNA. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) authorized the use of cidofovir for the treatment of cytomegalovirus retinitis in adults with acquired immunodeficiency syndrome only. Its use in RRP is off-label. It is not approved by the ANMAT for this indication either. Although usually used at cidofovir 5 to 7.5 mg/mL concentrations and up to 5 mL injection volumes, there is no consensus on the dose and optimal administration scheme or about its long-term adverse effects.PurposeTo assess the available evidence on the efficacy, safety and coverage related aspects regarding the use of cidofovir in patients with Recurrent Respiratory Papillomatosis.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsTwo systematic reviews, one RCT, two clinical practice guidelines and one coverage policy document were used to prepare this document.An RCT published in 2008 randomized 19 patients diagnosed with RRP to postsurgical treatment with intralesional cidofovir or placebo. With a 12-month follow up no significant differences were found between both groups when assessing the number or interventions performed annually, severity of the RRP, quality of life and voice defects.A systematic review published in 2011 included one RCT, two retrospective case-control studies and 27 case series. When assessing the case series, the rate of total remission reported with intralesional cidofovir was 53% (131 out of 247 patients). One case-control study published in 2009 (n=51 patients) reported a 53%-remission rate in patients receiving adjuvant intralesional cidofovir versus 90% in the no cidofovir group.Clinical Practice GuidelinesThe consensus of the American Pediatric Otolaryngology´s RRP taskforce recommends that intralesional injections of cidofovir should be used in patients requiring six or more surgeries a year, in those in which the interval between surgeries is decreasing, in children with extra-laryngeal involvement or having large papillomas.CostsThe international cost of one cidofovir vial is approximately $5,400 (Argentine pesos, February 2013) equivalent to US$1,100 (American dollars, February 2013).Coverage PoliciesOne Us health sponsor does not cover cidofovir for the treatment of PRR since this practice is considered investigational.ConclusionsThe use of cidofovir as adjuvant therapy in patients with RRP is based on low methodological quality evidence. The only RCT published did not show differences between the use of placebo and cidofovir.