Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups

British Journal of Cancer
H L McLeodJ Verweij

Abstract

Rhizoxin is a macrocyclic lactone compound that binds to tubulin and inhibits microtubule assembly. Rhizoxin demonstrated preclinical anti-tumour activity against a variety of human tumour cell lines and xenograft models. Phase I evaluation found a maximum tolerated rhizoxin dose of 2.6 mg m-2, with reversible, but dose-limiting, mucositis, leucopenia and diarrhoea. Clinical trials were then initiated by the EORTC ECSG in melanoma, breast, head and neck, and non-small-cell lung cancers with the recommended phase II rhizoxin dose of 2 mg m-2. Pharmacological studies were instituted with the phase II trials to complement the limited pharmacokinetic data available from the phase I trial. Blood samples were obtained from 69 of 103 eligible patients enrolled in phase II rhizoxin studies, and these were evaluable for pharmacokinetic analysis in 36 patients. Plasma rhizoxin concentrations were determined by high-performance liquid chromatography (HPLC), and post-distribution pharmacokinetic parameters were estimated by a one-compartment model. Rhizoxin was rapidly eliminated from plasma, with a median systemic clearance of 8.41 min-1 m-2 and an elimination half-life of 10.4 min. Rhizoxin area under the concentration-time curve (AUC) w...Continue Reading

Citations

Aug 13, 2008·The Journal of Infectious Diseases·Ashraf S IbrahimBrad Spellberg
May 14, 2010·Natural Product Reports·Jörn Piel
Jan 5, 2001·Angewandte Chemie·Gary E KeckVictor J Cee
Dec 6, 2005·Organic & Biomolecular Chemistry·Ian S MitchellJeffrey Stonehouse
Dec 13, 2006·Chembiochem : a European Journal of Chemical Biology·Laila P Partida-Martinez, Christian Hertweck
Jul 9, 2011·PLoS Pathogens·Gerald Lackner, Christian Hertweck
Dec 23, 2015·Natural Product Reports·Eric J N Helfrich, Jörn Piel
Oct 21, 2015·Analytical Cellular Pathology (Amsterdam)·Daniele FanaleViviana Bazan
Jun 20, 2019·Journal of Cellular Physiology·Sajad YaghoubiMeghdad Abdollahpour-Alitappeh
Feb 2, 2012·Chemical Society Reviews·Christian OttmannMarkus Kaiser
Nov 16, 2018·Angewandte Chemie·Pol KarierAlois Fürstner
Oct 13, 2011·ChemMedChem·Björn KusebauchChristian Hertweck
Jan 8, 2009·Journal of Natural Products·David G I Kingston
Apr 23, 2004·Organic Letters·Yueheng JiangSteven D Burke
Jul 12, 2019·Journal of Natural Products·Sylvia Kunakom, Alessandra S Eustáquio
Mar 14, 2019·Journal of Natural Products·Adam C CarterRobert H Cichewicz
Aug 31, 2006·Journal of the American Chemical Society·Kirstin ScherlachChristian Hertweck
Oct 26, 2002·The Journal of Organic Chemistry·James D WhiteBarton W Phillips
Oct 24, 2001·The Journal of Organic Chemistry·Steven D. BurkeAndrew P. Mongin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.