Clinical implications of N-(2-hydroxypropyl)methacrylamide copolymers.
Different anticancer drugs, farmorubicin, doxorubicin, paclitaxel and cis-platin have been conjugated through a Gly-Phe-Leu-Gly tetrapeptide side chain to a water-soluble synthetic polymeric carrier based on N-(2-hydroxypropyl)methacryalmide (HPMA) non-targeted or targeted with galactosamine and/or human IVIg and used in Phase I clinical trials. Conjugation of the drugs to the polymeric carrier that is non-toxic and non-immunogenic in man significantly decreased their non-specific organ toxicities and increased maximum tolerated dose up to 5 times. Macromolecular therapeutics based on HPMA have radically different pharmacokinetics. Drugs are not released from their polymeric carrier and remain in the peripheral blood and urine of patients mostly in their polymer-bound form. A clinical response against some refractory cancers was recorded in Phase I clinical trials. It was also demonstrated that doxorubicin-HPMA copolymer conjugates containing an immunoglobulin moiety have both cytostatic and immunomobilizing activity.
Ríhová
B
B
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142-20 Prague 4, Czech Republic. rihova@biomed.cas.cz
Kubácková
K
K
D000178:Acrylamides / Q000008:administration & dosage / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000178:Acrylamides; D000970:Antineoplastic Agents; D004337:Drug Carriers; C032976:N-(2-hydroxypropyl)methacrylamide