Phase I study of antisense oligonucleotide against vascular endothelial growth factor: decrease in plasma vascular endothelial growth factor with potential clinical efficacy

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Alexandra M LevineParkash S Gill

Abstract

Vascular endothelial growth factor antisense (VEGF-AS) is an antisense oligonucleotide that targets VEGF, inhibiting angiogenesis and tumor cell proliferation. This study established the safety, biologic effects, and pharmacokinetics of VEGF-AS in 51 patients with advanced malignancies. VEGF-AS was administered as a 2-hour infusion daily for 5 consecutive days for only one cycle on the first four dose levels, and then administered daily for 5 days every other week for up to 4 months on subsequent levels. Pharmacokinetics, tumor response, and the effect on plasma VEGF levels were determined. The maximum-tolerated dose was 200 mg/m2. Dose-limiting toxicities included grade 4 fever, and pulmonary embolism in one patient each at 250 mg/m2. Mild anemia, fever, fatigue, and gastrointestinal complaints were the most common adverse events. VEGF-AS t(1/2beta) (beta-phase terminal half-life of drug concentration) was 2.25 hours (range, 1.97 to 2.95 hours). Mean plasma VEGF-A (P = .002) and VEGF-C (P = .01) levels decreased 24 hours postinfusion, with a trend towards greater decreases at higher dose levels. At the maximum-tolerated dose, five of six patients demonstrated reductions in plasma VEGF. Clinical responses included complete remi...Continue Reading

References

May 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B D ChesonM J Keating
Sep 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S E KrownJ C Wernz
Jun 15, 1989·Biochemical and Biophysical Research Communications·N Ferrara, W J Henzel
Jan 1, 1994·Progress in Growth Factor Research·G NeufeldB Z Levi
Sep 1, 1993·Cancer Metastasis Reviews·D R SengerH F Dvorak
Oct 24, 1996·The New England Journal of Medicine·P S GillR C Gallo
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·R MasoodP S Gill
Aug 1, 1997·The American Journal of Surgical Pathology·S Y LeungL P Chung
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G AchenS A Stacker
May 12, 1998·Molecular Medicine Today·J M Gleadle, P J Ratcliffe
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B D ChesonG P Canellos
Mar 16, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gavin M MarxDavid Khayat
Mar 16, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bart C KuenenGiuseppe Giaccone
Dec 4, 2002·The Journal of Experimental Medicine·Janice A NagyHarold F Dvorak
Feb 21, 2003·International Journal of Cancer. Journal International Du Cancer·Rizwan MasoodParkash S Gill
Aug 19, 2004·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Weiguo XuChengla Yi

❮ Previous
Next ❯

Citations

Jul 14, 2006·Nature Reviews. Cancer·Adrian M JubbHartmut Koeppen
Dec 18, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J RuanJ P Leonard
Jun 5, 2007·Current Opinion in Oncology·Warren A Chow
Oct 10, 2012·Future Medicinal Chemistry·Lingyi HuangKejiang Lin
Aug 2, 2011·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Xing DaiRajiv Kumar Jha
Apr 25, 2007·Leukemia & Lymphoma·Kristen Ganjoo
Nov 16, 2006·Expert Opinion on Therapeutic Targets·Sofia BakaGordon C Jayson
Apr 27, 2011·Expert Opinion on Pharmacotherapy·Cecilia SgadariBarbara Ensoli
Sep 1, 2009·Expert Opinion on Drug Discovery·Carolyn A StatonMalcolm Wr Reed
Nov 19, 2013·Current Problems in Cancer·Joseph FinneyMarta Batus
Apr 29, 2015·Advanced Drug Delivery Reviews·Eric Wickstrom
Jun 9, 2012·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Mahnaz Fatahzadeh
May 14, 2011·Molecular Aspects of Medicine·Sònia TuguesLena Claesson-Welsh
Jul 16, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Minna TaskinenSirpa Leppä
Dec 10, 2009·Molecular Aspects of Medicine·Danielle Park, Pierre J Dilda
Feb 20, 2008·Leukemia Research·Semra PaydasGulsah Seydaoglu
Jul 11, 2008·Reviews in Medical Virology·Corey Casper
Mar 13, 2014·Critical Reviews in Oncology/hematology·Yvonne M H Versleijen-JonkersWinette T A van der Graaf
Sep 10, 2016·Cancer Treatment Reviews·Pedro BarataDavid S Hong
Feb 19, 2008·The British Journal of Surgery·A R JohnM C Eggo
Nov 2, 2016·The European Respiratory Journal·Marisa PerisUNKNOWN RIETE Investigators
Apr 2, 2008·The Oncologist·Hans GelderblomJudith V M G Bovée
Apr 5, 2019·Oncology Letters·Cristiana TanaseRadu Albulescu
Aug 31, 2017·Medical Oncology·Robin L JonesSeth M Pollack
Jun 27, 2008·Current Treatment Options in Neurology·Herbert B Newton
Jun 3, 2021·Cancers·Agnieszka E ZającPiotr Rutkowski
Sep 15, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·David H LinEmil P Kartalov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

HIV/AIDS-Related Malignancies

HIV/AIDS infection increases the risk of non-communicable diseases common in the aged including HIV/AIDS-related malignancies. Discover the latest research in HIV/AIDS-related malignancies.

AIDS Malignancies (ASM)

HIV infection increases the risk of non-communicable diseases common in the aged, including cardiovascular disease, neurocognitive decline, non-aids malignancies, osteoporosis, and frailty. Discover the latest research in AIDS malignancies.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.