The histopathologic effects of cidofovir on cartilage

Abstract

Problem: Intralesional injection of the nucleoside analog, Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cystosine], is used with increasing frequency as treatment for recurrent respiratory papillomatosis (RRP). While systemic toxicity of Cidofovir for other uses is somewhat known, the appropriate dosing for treatment of RRP, and toxic effects of Cidofovir on laryngeal cartilage and surrounding tissues have not been studied widely. We describe the histopathologic effects of Cidofovir, in various concentrations, on rabbit ear cartilage in vivo. Methods: Six adult New Zealand white rabbits were used. Under general anesthesia, the animals’ auricles were divided into 8 0.5 cm × 0.5 cm squares, demarcating standardized injection sites. Four different concentrations of Cidofovir in 0.1 cc normal saline (0mg/ml [control], 5.0mg/ml, 25.0mg/ml, and 75.0mg/ml) were injected twice each into the auricles just adjacent to the auricular cartilage. This provided 24 test sites for each concentration of the medication. Gross appearance of each injection site was monitored, and after 6 weeks, the injection sites were excised and sent for histopathologic evaluation. The slides were examined in a blinded fashion for changes in the cartilage and soft tissue at the injection sites. Results: The histopathologic effects of Cidofovir on cartilage in an animal model are described for various dose concentrations. Our results help characterize dosing and local toxicity of the medication when used intralesionally. Conclusion: Implications of these local effects for the current use of intralesional Cidofovir in the treatment of RRP in human beings are explored. Significance: Currently the safe injection concentration of Cidofovir for the treatment of RRP is a matter of conjecture. Because the larynx is composed of soft tissue over a cartilaginous framework, any affect of the medication on these tissues is significant. This study begins to address the critical issue of titrating dose to affect and toxicity for intralesional Cidofovir. Support: None reported.