Anticancer carrier-linked prodrugs in clinical trials.
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.
Kratz
Felix
F
Tumor Biology Center, Macromolecular Prodrugs, Freiburg, Germany. felix@tumorbio.uni-freiburg.de
Abu Ajaj
Khalid
K
Warnecke
André
A
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004337:Drug Carriers / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D015507:Drugs, Investigational; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D004337:Drug Carriers; D015507:Drugs, Investigational; D011355:Prodrugs