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CT-2103: Emerging Utility and Therapy for Solid Tumours

CT-2103: Emerging Utility and Therapy for Solid Tumours

Corey J Langer

Expert Opin Investig Drugs. 2004 Nov;13(11):1501-8.

PMID: 15500397

Abstract:

CT-2103 (XYOTAX, Cell Therapeutics, Inc.) is a conjugate of paclitaxel to a polyglutamate polymer. Its macromolecular nature exploits enhanced permeability and retention in tumour tissues. This compound is stable and inactive in aqueous solution and undergoes predominantly intracellular metabolism at the site where active paclitaxel is released. Because it does not require a Cremophor EL vehicle, it can be administered by short infusion into peripheral veins. In preclinical models, compared with the same dose of unconjugated paclitaxel in Cremophor EL-ethanol, CT-2103 yields >or= 12-fold increase in area under the curve in both plasma and tumour tissue. This alteration in drug pharmacokinetics and biodistribution is attributable to the ability of macromolecules to concentrate in areas of vascular leakiness, such as tumour tissue. CT-2103 is taken up by both tumour cells and normal phagocytic cells and is transported to lysosomes, where it is released by specific proteases through enzymatic action. In syngeneic and xenogeneic tumour models, at the maximally tolerated dose, CT-2103 appears to be more active than the standard doses of paclitaxel. It has also demonstrated activity in paclitaxel-resistant tumour models. Its potential enhancement of efficacy and decrease in drug-related toxicities make this agent an attractive option for therapeutic investigation. In Phase I trials it has been relatively well-tolerated, with acceptable toxicity at doses

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP126347748	Vinorelbine Related Compound A		126347-74-8 (free base)	Price

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