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Better Treatments for AIDS-Related Cancers Becoming Available

By Lawrence M. Prescott, Ph.D.

September 1997

According to investigators reporting on their findings at the recent 33rd Annual Meeting of the American Society of Clinical Oncology, more potent anti-retroviral agents, the usefulness of growth factors in HIV-infected persons, and more effective chemotherapeutic regimens all are leading to better treatment and control of AIDS-related cancers. Listed below are highlights of some of the more significant studies.

Systemic Therapy For KS Not Needed

With the availability of the protease inhibitors and more potent combined antiretroviral drug regimens which are able to produce sustained suppression of HIV, it appears that chronic therapy is no longer needed for many patients who previously required systemic therapy for epidemic Kaposi's sarcoma (KS), stated Dr. Mathew D. Volm, Kaplan Cancer Center, New York University Medical Center, New York, New York.

Although persons with early epidemic KS are managed with local therapy, those with advanced disease require systemic therapy with interferon or cytotoxic chemotherapy. Most patients show improvement with systemic therapy, but in the past, all have needed chronic long term treatment to control their disease, resulting in the discomfort and drug-related side effects of these drugs. With the development of more potent combination antiretroviral drug regimens, it appears that chronic therapy may not be needed for some patients.

In December 1996, a group of 16 patients (all of whom eventually achieved a viral load that was undetectable with effective anti-retroviral therapy(were identified who were able to stop systemic therapy for epidemic KS. No patient since December 1996 has experienced progression of KS and all persons continue off systemic therapy directed against KS. The median time off of systemic therapy is now 32 weeks (range 22 to 63 weeks). Overall, this group of individuals remains remarkably healthy and no patient has required hospitalization for any reason. Substantial and sustained increases in CD4+ lymphocyte counts have been observed for most of the group, with increases of more than 101 cells/ml.

Value of Colony Stimulating Factors Proven

A number of clinical studies now have pointed out that substances known as granulocyte-colony stimulating factors (G-CSF), manufactured by Amgen under the trade name NeupogenR, can help enhance the immune systems of HIV-infected cancer patients during chemotherapy.

When non-HIV-infected persons with cancer undergo chemotherapy, certain white blood cells called neutrophils are severely depressedand, until the level of these neutrophils are returned close to normal, chemotherapy must be delayed. This interrupts the normal pattern of treatment and may have a serious negative effect on the control or cure of the cancer. To overcome this difficulty, cancer patients are treated with G-CSF along with their chemotherapy. This speeds the recovery of the neutrophils and permits the treatment to proceed on schedule.

In HIV-infected persons, it had been thought that because of the action of the HIV virus on the immune system, the colony stimulating factors such as G-CSF would be of little help in returning neutrophil levels to normal. This does not appear to be the case and, in point of fact, G-CSF has been proven to be equally as effective in HIV-infected cancer patients as in non-HIV-infected persons.

Administration of chemotherapy along with G-CSF and erythropoietin (which enhances red blood cell production) proved to be highly effective and well tolerated for the treatment of AIDS-related non-Hodgkins lymphoma, stated investigators from the Cancer and Leukemia Group, Chicago, Illinois.

Overall, 45 persons received one of six regimens of increasing doses of cyclophosphamide, doxorubicin, vincristine, and etoposide, in conjunction with steroids, antiretrovirals, therapy for opportunistic infections (PCP, leptomeningeal, and fungal prophylaxis), G-CSF, and erythropoietin. In the 30 surviving patients, all of whom had high-grade cancers, there was an 80 percent response rate, more effective than ever before seen.

In a related study, according to Dr. Alexandra M. Levine, an AIDS and cancer expert at the University of Southern California Norris Cancer Hospital, Los Angeles, California, standard chemotherapy, when given in conjunction with G-CSF, is highly effective for the treatment of Hodgkin's disease in HIV-infected patients.

When 21 HIV-infected persons with Hodgkin's disease were treated with the standard chemotherapeutic regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine along with G-CSF, 80% of the treated patients responded to treatment. Unfortunately, survival was relatively short (19 months), but this was due to other HIV-related opportunistic infections rather than the cancer.

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