Conclusions
These data describing the preclinical and early clinical development of CT-2103 demonstrate the feasibility of using polyglutamic acid homopolymers to create macromolecular cytotoxic drug conjugates. PG has the characteristics of an ideal polymeric drug carrier including biodegradability, the ability to solubilise hydrophobic agents even at high loading, stability in circulation, and apparent lack of immunogenicity. Preliminary clinical data indicate that CT-2103 is well tolerated by short infusion and has what appears to be reduced toxicity to neural tissue and hair follicles compared with paclitaxel delivered in the standard formulation. In preclinical studies, the MTD was approximately twice that of standard paclitaxel and the antitumour efficacy in was improved. Preliminary clinical data from Phase II studies indicate that the MTD will be higher than that of paclitaxel and that CT-2103 has activity, even in patients who have failed prior taxane therapy. The potentially enhanced efficacy and apparently reduced toxicity of CT-2103 can be predominantly ascribed to its improved distribution to tumour tissue through the EPR effect and the reduced exposure of normal tissues. Taken together, these data suggest that PG is an excellent polymeric backbone for the delivery of oncologic therapeutics and is likely to improve the therapeutic indices of a number of other agents. A second PG conjugate designated CT-2106, a PG camptothecin with an interposed glycine linker, will enter clinical trials shortly.
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Singer, J.W. et al. (2004). Poly-(L)-Glutamic Acid-Paclitaxel (CT-2103) [XYOTAX™], a Biodegradable Polymeric Drug Conjugate. In: Maeda, H., Kabanov, A., Kataoka, K., Okano, T. (eds) Polymer Drugs in the Clinical Stage. Advances in Experimental Medicine and Biology, vol 519. Springer, Boston, MA. https://doi.org/10.1007/0-306-47932-X_6
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DOI: https://doi.org/10.1007/0-306-47932-X_6
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