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AIDS Treatment Update

TREATMENTS FOR KS: An overview of current treatment options for Kaposi's sarcoma




 

AIDS TREATMENT UPDATE, October 1995

Kaposi's sarcoma (KS) is an AIDS-defining illness that affects a substantial proportion of HIV-positive gay men and Africans. KS lesions can develop both inside and on the surface of the body. On the skin they look like brownish-red to purplish-black marks.

KS on the skin is not life-threatening, but visceral KS (involving the internal organs) can be. KS in the lymph nodes can obstruct normal fluid drainage leading to the body tissues to swell up painfully (oedema). KS in the lungs (pulmonary KS) can obstruct the airways causing a cough and breathlessness, and increases the risk of chest infections.

Many doctors and people with HIV are unwilling to treat KS that is restricted to a few skin lesions and causing no problems. If these are disfiguring, advice on camouflage make-up is available from many clinics and self-help groups. However, if you do decide to treat skin lesions, or your KS is severe enough that treatment is necessary (such as painful lesions on the soles of the feet), there is a range of options.

INTERFERON & RADIATION Radiation therapy can be used to treat KS lesions in the mouth or throat, painful skin lesions or lesions that are causing blockages in the lymph nodes of the face, arms and legs. The idea is to kill the over-active tumour cells with a series of low doses of radiation, leaving the rest of the body untouched. Side-effects can include short-term reddening of the skin and hair loss and, in the mouth, inflammation of the mucous membranes. The lesions usually leave a scar, like a mole, where pigmentation remains in the skin. This is particularly common when long-standing lesions are treated.

Interferon has been reported to be a helpful treatment for some people with KS. The best results have been seen when it is used by people with early KS, limited to the skin, at relatively high CD4 counts. Interferon has to be injected and usually causes side-effects of flu-like symptoms. It can also cause neutropenia - shortage of white blood cells called neutrophils which fight infections. This can leave the individual vulnerable to bacterial infections.

Alternatively, individual skin lesions can be injected with chemotherapy drugs, which causes the lesion to swell up painfully but then shrink or disappear, leaving a scar. Other approaches to treating skin lesions including removing them surgically or freezing them with liquid nitrogen.

CYTOTOXIC CHEMOTHERAPY Cytotoxic chemotherapy uses drugs that kill actively reproducing cells. They are used to treat cancers because cancerous cells reproduce at a high rate. The aim is to wipe out many cancerous cells without doing too much damage to normal, healthy cells.

In practice, chemotherapy tends also to damage the rapidly-dividing cells of the bone marrow, causing neutropenia. Some chemotherapy drugs have other unpleasant side-effects, including hair-loss and nausea.

Cancer doctors try to minimise these effects by selecting drugs that are least toxic to the bone marrow, including vincristine, vinblastine and bleomycin. These are used in combination and cause relatively few side-effects. They are somewhat effective, but after a period of time their effect may diminish and the KS may progress.

Researchers have also experimented with new formulations of chemotherapy drugs, which are designed to be less toxic. Two such drugs, liposomal doxorubicin and liposomal daunorubicin, are now approved for treating KS in the USA.

LIPOSOMAL TREATMENTS Liposomes are a method of enclosing a drug in microscopic bubbles of fat. These have several theoretical advantages.

First, the liposomes circulate in the bloodstream without releasing the drug. The drug is only released when the liposome leaves the bloodstream and lodges in the body tissues. This is most likely to happen within KS lesions, because the lesions are made up of a mass of abnormally growing blood vessels that are very 'leaky'. Thus, the chemotherapy is targeted to the lesions, wherever they are in the body, with less of the drug affecting non-cancerous areas and thus fewer side-effects.

Liposomal doxorubicin, also known by the tradename DOX-SL or DOXIL, is made by Sequus Pharmaceuticals (formerly known as Liposome Technology Inc.). Studies of liposomal doxorubicin found that the best dose is between 10 and 20 mg/m2 given every three weeks. Over 90% of treated people tend to have some reduction in the number or size of their KS lesions. This is difficult to compare with other trials as different methods are often used to measure the tumour burden (number, size and location of tumours).

The major side-effects are neutropenia, inflammation of the mouth (stomatitis) and hair loss. These are side-effects seen with the parent drug doxorubicin; however, doxorubicin's most serious side-effect of damage to the heart muscle is far less likely with the liposomal form. Some recipients have developed an unusual side-effect of ulcers on the hands and feet, known as hand-foot syndrome. Neutropenia caused by liposomal doxorubicin or other drugs can be treated with an agent such as G-CSF which promotes the growth of white cells.

At present liposomal doxorubicin is not approved in the UK, but doctors can obtain it on a named patient basis. Not all HIV centres currently offer treatment with liposomal doxorubicin but many may treat individuals with the drug if requested.

Another chemotherapy drug, daunorubicin, is used in liposomal form for treating KS, with similar response rates to liposomal doxorubicin. It is approved in the USA where it is manufactured by Vestar under the tradename DaunoXome, and available in the UK on a named patient basis.

In a study at the Kobler Centre which enrolled people with early KS, one group was treated immediately with liposomal daunorubicin and the other group received no treatment. The treated people had some improvement in their KS.

The results of trials comparing these liposomal drugs with conventional chemo-therapy treatments for KS are due to be presented at conferences in late September.

There has been no comparative trial of these two products so it is unclear which will prove to be the best. They have been anecdotal reports that people who have stopped responding to one liposomal drug may benefit from switching to the other.

EXPERIMENTAL TREATMENTS Several experimental treatments for KS are also currently being studied in the UK. In 1994 the results of experiments using mice with artificially induced KS lesions were reported. When female mice became pregnant, the KS lesions became smaller or disappeared altogether. Researchers found that a female hormone produced at high levels during pregnancy seemed to be killing the KS cells. A human form of this hormone, called human chorionic gonadotrophin (HCG) is already a licensed treatment for certain infertility problems.

Experiments using HCG as a treatment for people with KS have produced mixed results. One group of researchers said that injections of HCG caused lesions to shrink with few side-effects; other groups, including doctors in London, found that the injections had no obvious benefits but caused substantial side-effects, including irritability and anxiety serious enough to require psychiatric treatment. It is also very expensive.

A trial at St Mary's Hospital is testing an ointment called calcipotriol as a treatment for KS on the skin. For more information see the report in AIDS Treatment Update issue 28.

Over the last year evidence has been accumulating which suggests that KS may be caused by a virus that belongs to the herpes family. The virus, called KSHV or HHV-8, has consistently been found in cells taken from KS lesions. If KS is caused by this virus, drugs that inhibit that virus could help to treat KS.

One such treatment may be the anti-CMV drug foscarnet. In a small study, Swedish researchers found that people with early KS had reductions in the number and size of their KS lesions when treated with foscarnet, although the drug seemed to have no effects in people with advanced KS. A retrospective American study published earlier this year suggested that people who received anti-CMV treatment with foscarnet were also 70% less likely to develop KS compared to people who did not receive foscarnet, but a similar French study found no evidence of an anti-KS effect of foscarnet. A trial comparing foscarnet versus no treatment for KS is due to start later this year at three London clinics. In the meantime, however, doctors do not view foscarnet as a practical treatment for KS as it has to be administered intravenously and has serious side-effects.



 


Copy rights reserved to ATN 1995 AIDS Treatment News (ATN), the world's first treatment newsletter for people with HIV, reports on mainstream and alternative treatment, access to care, Web resources, public policy, and political action.



Information in this article was accurate in October 1, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.