Pediatric Recurrent Respiratory Papillomatosis: Fighting the Battle of a Rare But Serious Disease

Unlike interferon, cidofovir has not undergone rigorous efficacy trials or even extensive safety testing. The US Food and Drug Administration approved cidofovir for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients in 1996, prior to the development of effective anti-HIV therapies at a time when activists were demanding rapid approval of any agents that might work. Cidofovir has not been approved for other indications.

Numerous case series show that as many as two-thirds of pediatric RRP patients derive some benefit from the drug, which is injected into the surgical bed after removal of the papilloma. Typically, one-third of the patients show a dramatic improvement, with some having clinical resolution of their disease. Another third will show some limited improvement. The remaining patients show no improvement on therapy.

Craig S. Derkay, MD

Despite these positive results, experts express responsible skepticism because the drug has not been evaluated in a randomized placebo-controlled trial. Without that type of study, it is impossible to know what portion of a patient’s improvement is due to the drug and what is due to a change in the natural history of the disease.

Concern about the off-label use of cidofovir in RRP has increased following recent reports of a few patients treated with cidofovir whose disease progressed to cancer.

What we really need is a multicenter [randomized] study to look at the effectiveness, safety, and toxicity of cidofovir, said Dr. Derkay, but the company that makes it is perfectly happy to have ear, nose, and throat doctors use it off-label. It is not currently approved for the use of respiratory papilloma disease but they are not interested in putting the money into seeking FDA approval for it as a papilloma drug or accepting the liability for it if it turns out to be cancer-producing. So we are caught in a Catch-22. We have a drug that looks like it is a pretty good drug, but that is based on anecdotes and small patient series, and the safety data are actually a little scary-and we don’t have a company willing to bankroll the proper study that needs to be done.

Because of these safety concerns and the lack of demonstrated efficacy, the RRP Task Force has published a recommendation regarding the use of the drug. The committee agreed that the drug should be considered for use only in patients who require four or more surgeries per year or in whom the warts are starting to progress down the aerodigestive tract. In that case, the benefits of the drug may outweigh the risks. The drug, however, is not recommended for use in newly diagnosed patients for whom the natural history and aggressiveness of their disease is not yet apparent. Additionally, given that the drug has not been approved for use in RRP and there are safety concerns, physicians should go through an informed consent process with the parents of pediatric patients prior to administering the drug.