KS: New Treatment Possibilities

In January AIDS Treatment News (#73), reported on conventional treatments for Kaposi's sarcoma which have been adapted to HIV-related KS. Those included the careful use of radiation therapy, and chemotherapy administered intravenously or intralesionally. Recently, at least three more treatments have entered the field: the Prosorba column, interferon, and laser surgery.

The Prosorba column, also known as a protein A column, and the interferons alpha and beta are systemic approaches to KS (like intravenous chemotherapy). The use of lasers (like Velban injections or irradiation of specific lesion sites) is a localized treatment. Whether to consider a systemic treatment or a localized one depends on the growth and location of the lesions, as we described in the earlier article.

Lasers are currently being used to remove lesions in the mouth and esophagus, tissues which can become severely inflamed if treated with radiation. Herbert H. Dedo, M.D., of the University of California at San Francisco has used lasers for fifteen years to treat cancer and to remove warts or scar tissue. He feels that treatment of lesions in the oral cavity is warranted if they have become symptomatic--if they functionally impair swallowing or breathing. The procedure is done under general anesthesia and is usually followed by an overnight hospital stay. To gain access to the lesion, Dr. Dedo employs a retractor he designed himself, and with an operating microscope as a visual guide he aims a laser at the targeted lesion for a duration calculated in fractions of a second. The lesion is vaporized, and the surrounding blood capillaries are cauterized by the laser's action. The patient may experience some soreness at the site for a few weeks, but less than a surgical excision would cause.

The Prosorba column was first developed to treat cancer, and then was found to be useful against HIV-related ITP (idiopathic thrombocytopenic purpura). Dobri Kiprov, M.D., director of the plasmapheresis unit at Children's Hospital in San Francisco, has had over four years of experience using the Prosorba device for KS. He has seen a response rate (lesion regression or stabilization) of about 42%. The response in patients with ITP was higher, between 50 to 60%, but the KS application may still be refined to obtain a better result. The Prosorba column appears to be a simple procedure, but operates on a mechanism of action not fully understood. The object of this treatment is to remove from the bloodstream substances called circulating immune complexes (CIC), and other "blocking factors", which some researchers feel are an obstacle to a normal immune response.

According to this logic, the removal of some CIC could trigger an effective attack against the antigens responsible for KS and ITP. To accomplish this, a unit of blood is drawn from the patient and processed in a centrifuge, where cells are separated from plasma. The cells are returned unaffected to the patient, but the plasma is run through a column of silica which has been coated with "protein A". This protein binds with a type of immunoglobulin, the CIC targeted for removal. The plasma is then returned to the patient. Side effects appear to be slight but common--mostly fevers and chills. The treatment can be repeated periodically. Dr. Kiprov feels that circulating immune complexes may play a role in the development of ARC or AIDS, and that the Prosorba column, in addition to filtering out CIC, might potentiate the body's immunity by stimulating production of interleukin, and other components of the immune system. This treatment is still under investigation and is done under a research protocol.

Interferon is a protein naturally secreted by cells in response to viruses, bacteria, and other antigens. Occurring in
three distinct classes, alpha, beta and gamma, interferon stimulates surrounding cells to manufacture other proteins which in turn inhibit antigen growth or replication, and which enhance an appropriate immune response. It is the body's most rapidly produced defense. In related experiments, all the interferons demonstrated in vitro anti-HIV activity, and interferons alpha and beta were shown to have anti-tumor activity. At least 12 studies presented at the IV International Conference on AIDS in

Stockholm last June discussed the value of interferon as a treatment for KS. The results were uneven, but several reports suggested that interferon is more effective if given when T4-helper cell counts are over 200, and may work in synergy with AZT.

Last November the FDA approved the use of recombinant alpha interferon for treating KS, based on a lesion-reduction response in 40 to 45% of patients receiving a high dose. In December, AIDS Treatment News (#70) spoke with Mathilde Krim, Ph.D., founding co-chair of of the American Foundation for AIDS Research, who felt that the dose upon which the FDA based its approval was unnecessarily high: 20 million units or more daily. (The dose is usually lower when administered concurrently with AZT). Trials are still in progress which will hopefully determine the optimum therapeutic index (the ratio of an effective dose to a toxic dose). In any event, the side effects of large doses almost always include persistent flu-like symptoms.

Meanwhile, other potential KS treatments are being investigated, and we will watch for any good results. They include beta interferon, tumor necrosis factor, cryotherapy, colony stimulating factor, CL246,738 and interleukin-2.


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