GILL P, ARASTEH K, JACOBS M, FRIEDMAN-KIEN A, MILES S, GRACEY S, HANNAH A, LANGECKER P; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 488 (abstract no. 1160).
USC Norris Cancer Ctr., Los Angeles, CA
Angiogenesis is one of the most important features of AIDS-associated Kaposi's sarcoma (AIDS-KS). The strong expression of both Flk-1/KDR and flt-1 in small stromal vessels in and around tumors suggests that Vascular Endothelial Growth factor (VEGF) may be an important regulator of the edema and angiogenesis seen in Kaposi's sarcoma. SU5416 is a specific Flk-1 antagonist, decreasing VEGF-stimulated Flk-1 phosphorylation. Up to 30 patients with cutaneous AIDS-KS who are stable or progressed under current therapy will be treated with escalating doses of SU5416 administered twice weekly i.v. Starting dose was 65mg/m[2], escalated to 85, 110 and 145 mg/m[2]. Plasma levels of SU5416 and its metabolites, protease inhibitor levels, viral load and t-cell subset counts are being measured. Lesion size, extent of edema, as well as investigator and patient global assessments are performed at 4-week intervals. Response categorization is based on standard ACTG criteria. Patients are maintained on stable anti-retroviral therapy.To date, 16 HIV+ male patients with AIDS-related Kaposi's Sarcoma, ages from 31-47 (m=36), with KPS of 70-100 have received doses of SU5416 ranging from 65-145 mg/m[2] for up to 4 cycles of therapy (a cycle is 29 days). Among the first 9 patients in whom outcome could be assessed, 5 patients have evidence of biological activity (flattening, shrinkage or dissolution of lesions; reduction or dissolution of edema), 2 patients had stable disease and 2 patients had progressive disease. Individual patients showing response reported pain reduction and increased mobility. At the current dose, no dose-limiting toxicity has been observed to date. Individual patients treated at the higher doses reported mild headaches, which decreased with continued therapy. Several patients observed transient nausea. Two of the 16 patients discontinued treatment due to local toxicity at the site of SU5416 administration (which may be ameliorated by peripheral access device). SU5416 appears to have biological activity in AIDS-KS patients, even those that have failed multiple prior therapies. Side effects reported to date are mild to moderate and responsive to supportive care.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Angiogenesis Inhibitors
- Biomedical Research
- HIV Infections
- Humans
- Indoles
- Male
- Nausea
- Neoplasms
- Pyrroles
- SU 5416
- Sarcoma, Kaposi
- Skin Neoplasms
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor Receptor-1
- Vascular Endothelial Growth Factor Receptor-2
Other ID:
UI: 102245708
From Meeting Abstracts