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Title: DG DISPATCH - ASCO: Thalidomide Shows Activity In Renal Cell Carcinoma
URL: http://www.pslgroup.com/dg/1D311E.htm
Doctor's Guide
May 23, 2000


By Robert H. Carlson
Special to DG News

NEW ORLEANS, LA - May 23, 2000 -- Thalidomide's antiangiogenetic activity may be put to good use in treating renal cell carcinoma, a disease in which angiogenesis is crucial for development.

Researchers at the Kidney Cancer Center of San Francisco and at the University of New Mexico report that a patient with advanced, progressive metastatic renal cell cancer has responded with more than 50-percent shrinkage of the kidney tumor, a response which has lasted more than 11 months.

Laurence Elias, MD, Professor of Medicine and Chief of Hematology and Oncology, University of New Mexico, Albuquerque, presented data on a total of 15 patients at the 36th annual meeting of the American Society of Clinical Oncology, in New Orleans, LA.

Dr. Elias said thalidomide, the sleeping medication which gained notoriety in the 1950s because of its teratogenicity, is today being used to treat multiple myeloma and glioblastoma multiformae, as well as erythema nodosum and other uncommon inflammatory dermatologic conditions.

He said the high levels of VEGF and high levels of angiogenesis are thought to be particularly important in the development of renal cell carcinoma.

Basic research studies have shown that thalidomide has an antiangiogenic effect, as well as anticytokine effects, though exactly how this works against malignancies is unknown.

Dr. Elias said angiogenesis is thought to be particularly important in the development of renal cell because the VEGF growth-factor gene is in the pathway often disrupted by a gene deletion that is common in the typical clear-cell renal-cell carcinoma.

In this dose-finding study, which has recruited 15 patients out of a projected 30, one patient has tolerated thalidomide at up to 1,200 mg/day.

Dr. Elias said the patient, who had the definite partial response at the primary site, also had impressive reduction in pulmonary and hepatic metastases as well as necrosis in the renal primary.

Other patients in the study have had minor responses, he added, noting that this trial is recruiting a high proportion of previously-treated, poor-risk patients.

"We are still recruiting and with this small number of patients we cannot predict what the final response rate will be, but it appears that there may be some significant responses with this very novel agent and in this very difficult disease," Dr. Elias said.

The main side effects of thalidomide treatment have been somnolence, constipation and neuropathy, he said.

Agents commonly used to treat this difficult disease include the cytokine agents interleukin-2 and interferon-alpha.

"But there are no other conventional therapies, and cytotoxic chemotherapy been a big disappointment in this disease," Dr. Elias said.

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