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Anti-VEGF Agent Active Against Kaposi’s Sarcoma

Anti-VEGF Agent Active Against Kaposi’s Sarcoma

SAN FRANCISCO—Because Kaposi’s sarcoma is a highly vascular tumor, vascular endothelial growth factor (VEGF) may be a possible regulator for the edema and angiogenesis often seen in the disease, Parkash Gill, MD, of the Norris Cancer Center, University of Southern California, said at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

In this onging study, investigators are administered SU5416, a drug designed to interrupt VEGF-mediated signaling and decrease VEGF-stimulated phosphorylation. Patients with cutaneous AIDS-related Kaposi’s sarcoma that was stable or progressive under their current therapy receive escalating doses of SU5416 intravenously twice weekly. Patients begin with a dose of 65 mg/m², increasing to a maximum dose of 145 mg/m². The treatment is given in a cycle of 29 days, with a maximum of four cycles of therapy.

Patients are evaluated for antitumor response, plasma levels of SU5416 and its metabolites, protease inhibitor levels, viral load, and, especially, CD4 cell counts. Investigators also assess lesion size and extent of edema at 4-week intervals. Patients are maintained on stable anti-retroviral therapy.

Dr. Gill reported on 20 patients, all male, with a median age of 36 and median CD4 cell count of 272 cells/mm³. All but one patient had previously received protease inhibitors as part of their anti-HIV regimen. Nine patients had tumor-associated edema.

Five patients had a biologic response that included flattening and reduction of lesions and reduction of edema. Three patients had more than a 50% reduction in their tumor burden but did not sustain this for more than 4 weeks. Several patients showing a response reported increased mobility and a reduction in pain.

The one patient who had not received prior treatment with protease inhibitors showed a rapid response to therapy 4 weeks after treatment began, resulting in a complete flattening of lesions.

“For the most part, there was no impact on CD4 counts,” Dr. Gill said, “with rare cases showing a decline or increase in the numbers.” Similarly, there was no impact on HIV viral load.

The doses were well tolerated, although two patients discontinued therapy because of local toxicity at the site of dose injection. Headache, nausea, and vomiting were reported as the primary adverse effects at higher doses. These side effects decreased with continued therapy or supportive care. No dose-limiting drug toxicity was reported. “SU5416 is well tolerated and will be used in future trials,” Dr. Gill said.

 
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