Abstract
Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299. Adverse events typically observed with VEGF inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KS-associated herpesvirus DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KS-associated herpesvirus proliferation.
Publication types
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Clinical Trial, Phase I
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Research Support, N.I.H., Extramural
MeSH terms
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AIDS-Related Opportunistic Infections / drug therapy*
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Acquired Immunodeficiency Syndrome / drug therapy
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Adult
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DNA, Viral / blood
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Enzyme Inhibitors / adverse effects
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Enzyme Inhibitors / therapeutic use*
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Herpesvirus 8, Human / genetics
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Humans
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Imidazoles / adverse effects
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Imidazoles / therapeutic use*
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Interleukin-6 / blood
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Male
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Middle Aged
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Sarcoma, Kaposi / drug therapy*
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Thiazoles / adverse effects
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Thiazoles / therapeutic use*
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Vascular Endothelial Growth Factor A / antagonists & inhibitors*
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Vascular Endothelial Growth Factor A / blood
Substances
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DNA, Viral
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Enzyme Inhibitors
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IL6 protein, human
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Imidazoles
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Interleukin-6
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Thiazoles
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole
Supplementary concepts
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AIDS-related Kaposi sarcoma