Introduction

Most anti-cancer chemotherapeutic drugs used clinically are limited by a relatively low therapeutic index, owing to toxic side effects. - Over the past several decades, two strategies of improving the therapeutic efficacy of anti-cancer agents have emerged. The first approach is the design and development of agents that can modulate the molecular processes and pathways specifically associated with tumor progression. The success of this approach is shown by the successful introduction of a new breed of molecularly targeted anti-cancer agents such as imatinib mesylate (Gleevec), gefitinib (Iressa), trastuzumab (Herceptin), and cetuximab (C225, Erbitux). Alternatively, existing anti-cancer agents can be made more effective by using delivery systems that bring more drug molecules to the tumor site when compared with conventional formulation while reducing exposure of normal tissues to the drug. In this context, there have been important milestones with the use of polymer-drug conjugates in their own right. In particular, poly(l-glutamic acid) (PG)-paclitaxel (TXL) (CT2103, XYOTAX) has advanced to phase III clinical trials, and PG-camptothecin (CPT) (CT2106) has been tested in phase II clinical trials. The chemistry and applications of PG and its conjugates with various chemotherapeutic agents were previously reviewed.1 In this chapter, the applications of PG in the delivery of both chemotherapeutic and diagnostic agents will be updated. The results of clinical studies of XYOTAX and CT2106 will also be summarized. Previous chapters in this book discuss, in depth, the rationale for the use of polymeric conjugates as cancer therapeutics.

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