title: Paclitaxel poliglumex (XYOTAX; CT-2103): an intracellularly targeted taxane.
abstract: Paclitaxel poliglumex (CT-2103; XYOTAX) is an innovative macromolecular taxane designed to increase the therapeutic index of paclitaxel. This large macromolecule conjugate of paclitaxel and poly-L-glutamic acid accumulates in tumor tissues by taking advantage of the enhanced permeability of tumor vasculature and lack of lymphatic drainage. Paclitaxel poliglumex prolongs exposure to active drug and minimizes systemic exposure. Preclinical studies in animal tumor models demonstrate enhanced safety and efficacy relative to paclitaxel when administered as a single agent or in conjunction with radiation. Clinical pilot studies with paclitaxel poliglumex showed improved outcomes compared to standard taxanes and allowed a more convenient administration schedule. Human pharmacokinetic data are consistent with prolonged tumor exposure to active drug and a limited systemic exposure. Based on these results, three ongoing randomized phase III trials were initiated to test the efficacy of paclitaxel poliglumex in patients with advanced non-small cell lung carcinoma.
authors.affiliation: Cell Therapeutics, Seattle, WA 98119, USA. jsinger@ctiseattle.com
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
authors.forename: Scott
authors.initials: S
authors.lastname: Shaffer
authors.forename: Brian
authors.initials: B
authors.lastname: Baker
authors.forename: Alberto
authors.initials: A
authors.lastname: Bernareggi
authors.forename: Scott
authors.initials: S
authors.lastname: Stromatt
authors.forename: Drew
authors.initials: D
authors.lastname: Nienstedt
authors.forename: Marc
authors.initials: M
authors.lastname: Besman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D006207:Half-Life; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use* / Q000031:analogs & derivatives; D011099:Polyglutamic Acid / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000031:analogs & derivatives; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D011099:Polyglutamic Acid; D017239:Paclitaxel; C509139:paclitaxel poliglumex