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Phase I study of antisense oligonucleotide against vascular endothelial growth factor: decrease in plasma vascular
Alexandra M Levine1, Anil Tulpule, David I Quinn
1Department of Medicine, University of Southern California (USC), Keck School of Medicine, Los Angeles, CA 90033, USA. alevine@usc.edu
Summary
Vascular endothelial growth factor antisense (VEGF-AS) demonstrated safety and biologic effects in patients with advanced cancers. The drug showed preliminary clinical efficacy, including tumor response and prolonged survival, with manageable side effects.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Vascular Endothelial Growth Factor (VEGF) plays a crucial role in angiogenesis and tumor progression.
- Antisense oligonucleotides offer a targeted approach to inhibit specific gene expression.
Purpose of the Study:
- To evaluate the safety, biologic effects, and pharmacokinetics of VEGF-AS in patients with advanced malignancies.
- To determine the maximum-tolerated dose (MTD) of VEGF-AS.
Main Methods:
- VEGF-AS was administered via infusion in a dose-escalation study.
- Pharmacokinetic parameters, plasma VEGF levels, and tumor responses were assessed.
- Patients received treatment for up to 4 months.
Main Results:
- The MTD was determined to be 200 mg/m2.
- Common adverse events included mild anemia, fever, and fatigue.
- VEGF-AS administration led to significant reductions in plasma VEGF-A and VEGF-C levels.
- Preliminary clinical responses observed included complete remission and prolonged progression-free survival in some patients.
Conclusions:
- VEGF-AS is well-tolerated in patients with advanced malignancies.
- The drug exhibits biologic activity by reducing VEGF levels.
- VEGF-AS shows preliminary evidence of clinical efficacy, warranting further investigation.