AIDS TREATMENT NEWS No. 110 - September 7, 1990
Denny Smith

Radiation and Chemotherapy

Radiation was one standard approach to lymphoma discussed at the Sixth International Conference on AIDS in June. A three-year chart review of 25 cases of non-Hodgkin's lymphoma of the central nervous system was described by researchers from New York's Montefiore Medical Center/Albert Einstein College of Medicine[1]. All patients received total cranial irradiation; few side effects were noted and twelve patients showed symptom improvement. Subsequently, opportunistic infections claimed more lives than the lymphomas. Clinicians at the same institutions presented another chart review of 20 patients discussing various aspects of chemotherapy for lymphoma[2]. Although radiation or chemotherapy are often the most appropriate treatment choice and can achieve a complete tumor response in many people, they have a tendency to further impair the immune system by damaging the bone marrow's capacity to generate new blood cells. The authors of this abstract elaborated on the danger, suggesting that bone marrow toxicity from more than two cycles of chemotherapy may increase the chance of developing an opportunistic infection.

The authors also note that the risk for lymphomas appearing in the central nervous system, which is largely impervious to intravenous chemotherapy, warrants a chemotherapy prophylaxis, which is administered intrathecally (injected into the cerebrospinal fluid), to people under treatment for AIDS-related lymphoma.

We spoke to Lawrence Kaplan, M.D., and James Kahn, M.D., who supervise the lymphoma protocols at San Francisco General Hospital, and who discussed with us the current results from several lymphoma studies there.

Dr. Kahn described good responses from a chemotherapy regimen treating Hodgkin's disease: tumor regression, and little toxicity, was obtained from a combination of four chemotherapeutic agents -- bleomycin, vincristine, streptozocin, and etoposide. Hodgkin's disease is much less common among AIDS-related cancers, however, than non-Hodgkin's lymphoma.

Another study at San Francisco General involved a new drug called chlorodeoxyadenosine (CDA), which was given to nine people who had failed standard chemotherapy for non-Hodgkin's lymphoma. Two partial responses were obtained from this agent; Dr. Kaplan surmised that CDA could be more useful in combination with other drugs.

Controlling Toxicity: GM-CSF

Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) is perhaps the best-known of many human growth factors now under investigation. GM-CSF is already widely considered to be useful for controlling the bone-marrow toxicity of such treatments as AZT, ganciclovir, and interferon. A trial at San Francisco General comparing lymphoma chemotherapy regimens with and without GM-CSF found that neutropenia, a common side-effect of chemotherapy, was reduced for those participants receiving GM-CSF3. This abstract reported an initial drop in p24 antigen levels for both groups in the study, probably because of cell killing by the chemotherapy drugs.

We interviewed Dr. Kaplan, who gave us later information not included in the abstract. The group receiving GM-CSF required fewer hospitalizations, due to the reduction in neutropenia. However, after falling in both groups, the p24 level later rose above baseline in the group receiving GM-CSF with chemotherapy, but not in the group treated with chemotherapy alone. Neither group was receiving AZT or other anti-HIV drugs. Dr. Kaplan cautioned that this is a laboratory observation, not a finding in a clinical care setting.

Other Approaches

San Francisco General was also the site of a trial examining anti-idiotype antibody therapy, a relatively new technique to enhance a natural anti-tumor mechanism of the immune system. Dr. Kaplan said that because of the difficulty identifying tumors with shared idiotypes, this approach was largely unsuccessful. Other "immune-based" therapies are likely to be developed in the future for treating lymphoma. But for now, the practical question is whether chemotherapy is more effective and less toxic when given in low doses, or in large doses with GM-CSF used to control side-effects.

An important consideration during treatment for lymphoma, as with treatment for opportunistic infections, is the continuation of some anti-HIV therapy. But the combined toxicities of chemotherapeutic drugs and AZT or ddI can make this goal difficult to maintain. Dr. Kaplan suggests designing a treatment combination which avoids parallel toxicities, such as from vincristine and ddI.

References

1. Goldstein J, Dickson D, Valentine E, Davis L. Radiation therapy of the central nervous system in AIDS related non-Hodgkin's Lymphoma. Sixth International Conference on AIDS, June 1990, abstract #2102.

2. Sparano J, Goldstein J, Gucalp R, Davis L, Wiernik P. Patterns of failure and toxicity of chemotherapy in AIDS related non- Hodgkin's Lymphoma. Sixth International Conference on AIDS, June 1990, abstract #2092.

3. Kaplan L, Kahn J, Crowe S, Volberding P, Grossberg H, McManus N, Mills J. A randomized trials of chemotherapy with or without recombinant granulocyte monocyte colony stimulating factor in HIV-associated non-Hodgkin's lymphoma. Sixth International Conference on AIDS, June 1990, abstract #S. B. 510.

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