University of Wolverhampton
Browse
Collection All
bullet
bullet
bullet
bullet
Listed communities
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet

Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Cancer Research Group > Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/29455
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.
Authors: Seymour, Leonard W.
Ferry, David R.
Anderson, David
Hesslewood, Stuart
Julyan, Peter J.
Poyner, Richard
Doran, Jayne
Young, Annie M.
Burtles, Sally
Kerr, David J.
Citation: Journal of Clinical Oncology, 20(6): 1668-1676
Publisher: American Society of Clinical Oncology
Journal: Journal of Clinical Oncology
Issue Date: 2002
URI: http://hdl.handle.net/2436/29455
PubMed ID: 11896118
Additional Links: http://jco.ascopubs.org/cgi/content/full/20/6/1668
Abstract: PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2. PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine. Targeting, toxicity, and efficacy were evaluated in 31 patients with primary (n = 25) or metastatic (n = 6) liver cancer. Body distribution of the radiolabelled polymer conjugate was assessed using gamma-camera imaging and single-photon emission computed tomography. RESULTS: The polymer was administered by intravenous (i.v.) infusion over 1 hour, repeated every 3 weeks. Dose escalation proceeded from 20 to 160 mg/m(2) (doxorubicin equivalents), the maximum-tolerated dose, which was associated with severe fatigue, grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after administration, 16.9% +/- 3.9% of the administered dose of doxorubicin targeted to the liver and 3.3% +/- 5.6% of dose was delivered to tumor. Doxorubicin-polymer conjugate without galactosamine showed no targeting. Three hepatoma patients showed partial responses, with one in continuing partial remission 47 months after therapy. CONCLUSION: The recommended PK2 dose is 120 mg/m(2), administered every 3 weeks by IV infusion. Liver-specific doxorubicin delivery is achievable using galactosamine-modified polymers, and targeting is also seen in primary hepatocellular tumors.
Type: Article
Language: en
MeSH: Antineoplastic Agents
Area Under Curve
Chromatography, High Pressure Liquid
Doxorubicin
Drug Carriers
Female
Galactosamine
Gamma Cameras
Humans
Infusions, Intravenous
Liver Neoplasms
Male
Polymethacrylic Acids
Tomography, Emission-Computed, Single-Photon
Treatment Outcome
ISSN: 0732-183X
Appears in Collections: Cancer Research Group

Files in This Item:

There are no files associated with this item.



Related articles on PubMed
bullet
Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer Research Campaign Phase I/II Committee.
Vasey PA, Kaye SB, Morrison R, Twelves C, Wilson P, Duncan R, Thomson AH, Murray LS, Hilditch TE, Murray T, Burtles S, Fraier D, Frigerio E, Cassidy J
1999 Jan
bullet
Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.
Julyan PJ, Seymour LW, Ferry DR, Daryani S, Boivin CM, Doran J, David M, Anderson D, Christodoulou C, Young AM, Hesslewood S, Kerr DJ
1999 Feb 22
bullet
bullet
bullet
Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer.
DiPaola RS, Rinehart J, Nemunaitis J, Ebbinghaus S, Rubin E, Capanna T, Ciardella M, Doyle-Lindrud S, Goodwin S, Fontaine M, Adams N, Williams A, Schwartz M, Winchell G, Wickersham K, Deutsch P, Yao SL
2002 Apr 1
See all 140 articles

All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Fairtrade - Guarantees a better deal for Third World Producers

University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY

Course enquiries: 0800 953 3222, General enquiries: 01902 321000,
Email: enquiries@wlv.ac.uk | Freedom of Information | Disclaimer and copyright | Website feedback | The University as a charity

OR Logo Powered by Open Repository | Cookies