KAPOSI'S SARCOMA: A WIDE TREATMENT SPECTRUM EMERGING

Kaposi's sarcoma occurs in about 35* of all AIDS patients. The lesions of Kaposi's usually appear on the skin and must be biopsied to confirm a diagnosis. Recently, the frequency of new KS cases has decreased. More new treatments have become available, and older standard therapies for pre- epidemic KS have been adapted to deal with certain problems of AIDS-related KS.

The treatments reviewed here are fresh applications of conventional therapy. We will look at some new KS treatments in an upcoming issue of AIDS TREATMENT NEWS. No single agent, new or newly- adapted, has yet worked conclusively. But there are combinations which appear effective in specific stages of lesion growth. Several important factors help determine when and how to proceed against KS: the location of individual lesions, their rate of
progression, the advantages of treatments weighed against their drawbacks, and the compatibility of a KS treatment choice with HIV drugs or treatments which one may require for another opportunistic infection.

Where do the lesions appear? They may be localized, especially around the face or lower legs, or widely dispersed, and may involve internal organs. Treatment is definitely warranted if the lesions cause functional impairment, as with swallowing difficulties due to oral lesions, or pain from walking on a foot swollen from lymphatic involvement. Some
lesions are treated for cosmetic reasons. For either cosmetic or functional improvement, small cutaneous (skin) lesions can be directly injected with a dilution of vinblastine (Velban), a chemotherapeutic agent. Administered weekly or biweekly for several treatments, these intralesional injections may cause temporary inflammation but can stop or even reverse the growth of some lesions.

Lesions which are coalescent (merging together), or are too large for injection, or located in areas which are difficult to inject such as the eyelids or the bottom of the feet, should be treated with local radiation. We spoke with Dennis Hill, M.D., of Davies Medical Center in San Francisco regarding his application of radiotherapy for treatment of KS. He
has used radiation effectively with careful dose volume and frequency for localized treatment of cutaneous lesions, and for edema, or swelling, due to internal obstruction of the lymphatics. He cautions that large volume radiation which may aggravate the underlying immune deficiency is not justified. In addition, too much irradiation of oral lesions can
cause a serious inflammatory reaction in mucous tissue. But applied carefully, radiotherapy can obtain good palliative results (relief of symptoms) in many situations. Dr. Hill published his approach in Seminars in Oncology, Vol 14, No 2, 1987. Reprints of the article can be requested from the Department of Radiation Oncology, Davies Medical Center, Castro and Duboce, San Francisco, CA 94114.

How aggressive are the lesions ? If there are very few lesions and they appear stable, they may not warrant the risk of various unwanted treatment side effects. But if new lesions appear to be progressing rapidly in size or number, they should be treated before they become a functional or cosmetic problem. To inhibit rapid progression, or to deal with
slower lesions for which Velban injections or radiotherapy are not useful, a systemic approach with chemotherapy might be considered.

The most commonly used agents against AIDS- related KS are vincristine, vinblastine, etoposide, doxorubicin (Adriamycin), and bleomycin. There is evidence and general agreement that a combination of some of these drugs is more successful than any one used singly, but there is no consensus for which combination, dosage or frequency. The best combination would obtain an effective cytotoxic strength (able to kill KS cells) without corresponding damage to healthy tissue. For example, in addition to their anti-KS activity, vinblastine, etoposide, and doxorubicin can each suppress bone marrow production (myelosuppression), etoposide and doxorubicin are associated with alopecia (hair loss), and vincristine can cause neuropathy. One solution is to alternate the administration of different agents to avoid cumulative toxicity while maintaining anti- tumor effect. Another approach is to balance the dose and frequency such that multiple agents can be used simultaneously.

We interviewed Ivan Silverberg, M.D., also of Davies Medical Center in San Francisco. Dr. Silverberg has obtained good responses with a combination of 1 mg vincristine, 3 mg vinblastine, and 5 units bleomycin, given intravenously once a week. The side effects may include a fever after the infusion, and some minimal hair loss. He has not seen any serious toxicity with this ratio. One friend of ours adapted this combination to 1/2 mg vincristine and 2 mg vinblastine with 5 units bleomycin and after three months decreased the injections to once every two weeks. He felt that his lesions were completely stabilized.

In recent months, two different AIDS newsletters published their own thorough coverage of KS treatment options with a large focus on chemotherapy. Allen Maniker, M.D., wrote for the October 20th, 1988 Treatment Issues, published by
the Gay Men's Health Crises, 129 West 20th St., N.Y., NY 10011. Lawrence Kaplan, M.D., was the author of an article in the January 1989 "AIDS Medical Report"", published by American Health Consultants in Atlanta, 800/554-1032. Both articles provide a detailed background for people making treatment choices for KS.

How can these choices be integrated into a workable program of AIDS treatments? With any HIV-related illness, the root problem is an immune deficiency, so treatment choices must aim carefully to avoid further damage to the immune system. The optimum treatment program would include anti-HIV treatments and possibly an immunomodulator if
blood counts call for them and if they are chosen for compatibility with the appropriate KS therapy. Sometimes there is a conflict of treatment strategy between an HIV drug such as AZT and an anti-KS agent like doxorubicin, because they both suppress bone marrow production. But AZT can be administered safely with radiotherapy or non- myelosuppressive drugs such as vincristine.

We have heard reports of people with Kaposi's sarcoma being refused treatment on the assumption that it progresses too slowly to be of concern, or that there are no effective treatments anyway. But many physicians and patients have successfully stabilized lesion growth with flexible combinations of intralesional injections, radiation or chemotherapy.
In a future article we will compare new and investigational KS treatments, including interferon, laser therapy and the prosorba column.