Nonsurgical Treatment of Recurrent Respiratory Papillomas
The standard treatment for recurrent respiratory papillomas (RRP) is surgical resection. As described in the linked page, this can be done using several techniques but often must be repeated at regular intervals due to the high rate of recurrence for RRPs. For individuals who have severe disease necessitating frequent operations, there has been some success with non-surgical methods based on several different medications. This page will describe several of these.
Interferon
Interferons are glycoproteins with broad antiviral properties. For treatment of laryngeal papillomas, interferon is usually initially given on a daily basis as an intramuscular injection. Studies have varied somewhat in the dose, but the best results seem to be obtained if the injections are continued once a day for about a month and then dropped back to every other day for twelve months.
In a study of inteferon in 66 patients published in 1991, roughly one-third of the patients had complete resolution of their symptoms, one-third had a partial response that lasted an average of 400 days, and one-third had no response. The exact mechanism of the action was not known, and in most cases the drug was well tolerated.
Interferon can produce flu-like side effects, including fatigue, muscle aches, and headaches. These symptoms usually go away after the medicine is stopped. Unfortunately, in some individuals the papillomas recur quite quickly once the interferon has been discontinued.
Indole-3-Carbinol
One of the newest medications that has been used against papillomas is indole-3-carbinol (I3C). Research has shown that one of the breakdown products of estrogen, called 16 alpha hydroxyestrone, increases papilloma formation. The biochemical pathway that causes this reaction is believed more active in the larynx of individuals with HPV infection. I3C works by decreasing the activity of this reaction and shifting it towards formation of another product called 2 methyl estrone. This other breakdown product does not promote papilloma growth.
I3C is given in oral form as a twice-a-day pill. It is well tolerated, but has produced some dizziness when taken at inappropriately high doses.
Results of a preliminary study were quite similar to those for interferon quoted above: about one-third of the patients had a complete resolution of their papillomas, one-third had a partial response, and one-third had no response. Additional studies are underway to compare the effectiveness of I3C with other treatment methods.
Cidofovir
Cidofovir is an antiviral medication approved by the FDA for treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. It has been shown to be active against a wide variety of herpes viruses, an early reports also show that it is successful in treating laryngeal papillomas. The medication is administered by direct injection into the papillomas. To date there have been promising trial studies, and other investigational studies are underway.
Photodynamic Therapy
Photodynamic therapy (PDT) is a combined treatment in which a special medication is first given and then, after a certain time delay, the papillomas are treated with light. The medicine used has two special properties: it is taken up in higher concentration in papillomas, and it becomes toxic when activated by light of a certain wavelength.
The medication that has been most extensively used for PDT is called dihematoporphyrin ether (DHE; the trade name is Photofrin II). DHE is given intravenously (by vein) and the light treatment is usually done 24-48 hours afterwards. This time delay maximizes the concentration of DHE in the papillomas. DHE is strongly activated with red light at a wavelength of 630 nm. A laser is usually used as the light source since certain lasers can be tuned to produce light at a very specific wavelength. Unlike carbon dioxide lasers that burn off the papillomas, the light in PDT is much less intense and is instead used to activate a chemical reaction that then kills the papilloma cell. (Without the PDT, the light alone would have minimal effect on the papillomas).
The dose effect of PDT depends primarily on a combination of the amount of drug given, the intensity of the laser light, and the length of time the light is exposed on the papilloma. Usually treatment times of about 3-5 minutes are used. The light is usually transmitted through a optical fiber placed a certain distance above the tissue. If the papillomas are quite extensive, multiple sites can be treated at one setting. For large papillomas, the fiber can be inserted right into the papilloma.
Precise dosing in PDT is, from a practical standpoint, quite difficult. It is hard to predict how much light energy is transmitted to deeper tissue and the concentration of the drug in the tissue is also hard to predict. Dosages also depends on the distance between the end of the fiber and the papilloma, and this may be hard to keep constant given the complex anatomy of the larynx.
The major drawback of PDT is that most of the photosensitive drugs also produce sensitivity to sunlight. After administration of these drugs, individuals need to stay out of the sun for up to six weeks. Exposure to the sun can cause burns, swelling, itching, and increased skin pigmentation. As a result, there is ongoing research trying to find better photosensitive drugs that either cause fewer side effects or have better selective uptake in the papillomas.
Other Method and Medications
Other medications have also been used against papillomas with mixed results. Acyclovir is a commonly used viral infections used most often for Herpes simplex. Although the papilloma virus does not contain the protein against which acyclovir is targeted, a pilot study has shown some effectiveness with laryngeal papillomas.
Methotrexate, a strong chemotherapy drug often used for head and neck cancer, has been used in a very small number of cases of laryngeal papillomas. It showed promise in these few patients, but has not been extensively studied for this disease.
Isotretinoin is one of a group of drugs called retinoids that have been shown to slow down the proliferation of normal and abnormal cells. Some studies have shown that isotretinoin is effective against HPV but in other cases it had no effect on their growth.
|
