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Publications à Abstracts |
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Anticancer
carrier-linked prodrugs in clinical trials Felix
Kratz Expert Opinion on
Investigational Drugs, 2007, 16 (7), 1037–1058 Keywords:
antibodies, anticancer prodrugs, cancer chemotherapy,
drug targeting, polymer therapeutics Abstract: Coupling of low molecular
weight anticancer drugs to antibodies, serum proteins or polymers through a
cleavable linker has been an effective method for improving the therapeutic
index of cytotoxic established agents. Modern
drug–antibody conjugates that have recently entered clinical trials have
primarily used highly potent drugs such as calicheamicin
or maytansins. Gemtuzumab
ozogamicin, a conjugate of calicheamicin
and an anti-CD33 humanized antibody, is the first drug–antibody conjugate to
receive market approval. Drug conjugates that have undergone clinical
assessment include N-(2-hydroxypropyl)methacrylamide
(HPMA) copolymer conjugates with doxorubicin, camptothecin,
paclitaxel and Pt(II) complexes, poly(ethylene
glycol) conjugates with camptothecin and paclitaxel, polyglutamate
conjugates with paclitaxel and camptothecin,
a methotrexate–albumin conjugate and an
albumin-binding doxorubicin prodrug. This review
summarizes the Phase I – III studies that have been performed with these
macromolecular prodrugs |
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