Combretastatin A4 phosphate: background and current clinical status

Expert Opinion on Investigational Drugs
Scott L Young, David J Chaplin

Abstract

Combretastatin A4 phosphate (CA4P) represents the lead compound in a group of novel tubulin depolymerising agents being developed as vascular targeting agents (VTAs). VTAs are drugs that induce rapid and selective vascular dysfunction in tumours. CA4P is a water-soluble prodrug of the cis-stilbene CA4 originally isolated from the tree Combretum caffrum. Preclinical studies have shown that CA4P induces blood flow reductions and subsequent tumour cell death in a variety of preclinical models. Moreover, this activity has been linked to its ability to rapidly alter the morphology of immature endothelial cells by disrupting their tubulin cytoskeleton. Phase I clinical trials have established a maximum tolerated dose in the range 60-68 mg/m2 and in addition have established that significant changes to tumour perfusion can be achieved across a wide range of doses. The dose-limiting toxicities include tumour pain, ataxia and cardiovascular changes. The maximum tolerated dose was independent of schedule, indicating the absence of cumulative toxicity. Although unexpected from preclinical studies, some evidence of clinical response was seen using CA4P as a single modality. Based on the Phase I data, combination studies of CA4P with establ...Continue Reading

References

Jan 1, 1991·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B C BaguleyL J Zwi
Mar 1, 1989·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·M R HorsmanJ Overgaard
May 1, 1987·Journal of Natural Products·G R PettitS B Singh
Apr 1, 1995·British Journal of Cancer·J A WoodsA T McGown
Jan 1, 1994·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·D J Chaplin, M R Horsman
Dec 9, 1998·International Journal of Radiation Oncology, Biology, Physics·R J MaxwellM R Horsman
Dec 9, 1998·International Journal of Radiation Oncology, Biology, Physics·M R HorsmanJ Overgaard
Dec 9, 1998·International Journal of Radiation Oncology, Biology, Physics·L LiD W Siemann
Feb 23, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·M R Stratford, M F Dennis
Dec 22, 1999·British Journal of Cancer·K GrosiosM C Bibby
Mar 4, 2000·International Journal of Radiation Oncology, Biology, Physics·H P EikesdalO Dahl
Aug 24, 2000·International Journal of Cancer. Journal International Du Cancer·A S BöhleD Henne-Bruns
Feb 15, 2001·International Journal of Radiation Oncology, Biology, Physics·W LanduytP Lambin
Mar 22, 2001·British Journal of Cancer·J GriggsE D Williams
Jul 6, 2001·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H P EikesdalO Dahl
Jul 6, 2001·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·R MurataM R Horsman
Mar 14, 2002·The American Journal of Pathology·Jeremy GriggsRobin Hesketh
Apr 12, 2002·International Journal of Cancer. Journal International Du Cancer·Dietmar W SiemannAmyn M Rojiani
Jun 13, 2002·International Journal of Experimental Pathology·Gillian M TozerSally A Hill
Dec 3, 2002·International Journal of Radiation Oncology, Biology, Physics·David J Chaplin, Sally A Hill
Dec 3, 2002·International Journal of Radiation Oncology, Biology, Physics·Michael R Horsman, Rumi Murata
Feb 21, 2003·Thyroid : Official Journal of the American Thyroid Association·Joshua M DzibaKenneth B Ain
Jun 17, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gordon J S RustinPatricia M Price
Jun 17, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Helen L AndersonPatricia M Price
Jun 17, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Susan M GalbraithGordon J S Rustin
Jul 29, 2003·Investigative Ophthalmology & Visual Science·Hiroyuki NambuPeter A Campochiaro
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James P StevensonPeter J O'Dwyer
Jan 20, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H WildiersA T van Oosterom
Mar 1, 1948·British Journal of Cancer·R J LUDFORD

❮ Previous
Next ❯

Citations

Jun 22, 2007·Cancer Chemotherapy and Pharmacology·Daniele MartarelliGiovanni Mazzoni
Dec 17, 2008·Cancer Chemotherapy and Pharmacology·Flaubert Mbeunkui, Donald J Johann
Jan 28, 2009·Pharmaceutical Research·Christopher B PattilloMohammad F Kiani
Apr 28, 2010·Journal of Medicinal Chemistry·Romeo RomagnoliGiampietro Viola
Jun 2, 2005·Nature Reviews. Cancer·Gillian M TozerBruce C Baguley
Jun 15, 2011·Journal of Medicinal Food·Marcos G S GouveiaLucindo J Quintans-Júnior
Apr 21, 2007·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Peter F KadorMilton Wyman
May 22, 2009·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Li MaQiang Zhang
Aug 8, 2006·American Journal of Clinical Oncology·Alexandra GiatromanolakiMichael I Koukourakis
Feb 19, 2010·The Cancer Journal·Sally Greenberg, Hope S Rugo
Apr 15, 2011·Journal of Drug Delivery·Maluta S MufamadiValence M K Ndesendo
Apr 27, 2011·Cancer Cell International·M Janaki RamaiahManika Pal Bhadra
Jun 27, 2006·The AAPS Journal·Young-Won ChinA Douglas Kinghorn
Apr 6, 2006·AAPS PharmSciTech·Mikko JuutiTuula T Pakkanen
Nov 11, 2011·International Journal of Nanomedicine·Mengen ZhangXiangyang Shi
Jun 1, 2013·Thyroid : Official Journal of the American Thyroid Association·Julie A SosaScot C Remick
Apr 1, 2014·European Journal of Medicinal Chemistry·Mohamed Ali SoussiMouad Alami
Oct 10, 2008·The British Journal of Radiology·G M TozerS A Hill
Dec 10, 2013·Expert Opinion on Therapeutic Patents·Yi-Min LiuJing-Ping Liou
Mar 1, 2007·Expert Opinion on Drug Discovery·Nadine DarwicheHala Gali-Muhtasib
Oct 1, 2007·Expert Opinion on Drug Discovery·Dietmar W Siemann, David J Chaplin
Jun 23, 2009·Expert Opinion on Drug Delivery·Bei ChenKaichun Wu
Oct 30, 2009·Journal of Drug Targeting·Robert PolaBlanka Ríhová
Oct 12, 2014·Experimental Eye Research·Rania S SulaimanTimothy W Corson
Oct 30, 2012·Experimental Parasitology·Manlio TolomeoClaudia Colomba
Sep 18, 2012·European Journal of Medicinal Chemistry·Ahmed KamalManika Pal-Bhadra
Jul 20, 2010·Bioorganic & Medicinal Chemistry Letters·Ahmed KamalManika Pal-Bhadra
Mar 17, 2010·Phytochemistry Letters·Li PanA Douglas Kinghorn
Mar 10, 2016·Experimental Parasitology·Germano CastelliManlio Tolomeo
Jan 2, 2009·Cancer Treatment Reviews·April L RisingerSusan L Mooberry
Jan 2, 2007·Bioorganic & Medicinal Chemistry Letters·Laixing HuDavid W Boykin
Oct 31, 2006·Bioorganic & Medicinal Chemistry·John W Lippert
Apr 28, 2007·Medicinal Research Reviews·Bhabatarak BhattacharyyaMithu Banerjee
Sep 29, 2011·Rapid Communications in Mass Spectrometry : RCM·Joanna E Barbara, Jose M Castro-Perez

❮ Previous
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