Anticancer carrier-linked prodrugs in clinical trials

Expert Opin Investig Drugs. 2007 Jul;16(7):1037-58. doi: 10.1517/13543784.16.7.1037.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Carriers / pharmacology
  • Drug Carriers / therapeutic use*
  • Drug Delivery Systems
  • Drugs, Investigational*
  • Female
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Drugs, Investigational
  • Prodrugs