Conclusion
The pharmacokinetics of DX-8951f were greatly improved by DE-310 with the extremely longer retention in bloodstream, resulting in the preferential tumor-targeting, and with the slow release appropriate to camptothecin analog DX-8951f in tumor tissue. On the basis of the pharmacokinetic improvement, DE-310 exhibited enhanced antitumor effects with reduced toxicities by a single and low dose, compared with DX-8951f. These preclinical results suggest that DE-310 is a promising agent for cancer treatment. The phase I trials are still ongoing and recently, the interim clinical data have been reported15, 16.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ringsdorf, H., 1975, Structure and properties of pharmacologically active polymers. J. Polym. Sci. Polym. Symp. 20: 135–153.
Matsumura, Y., and Maeda, H., 1986, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism and antitumor agent smancs. Cancer Res. 46: 6387–6392.
Maeda, H., Wu, J., Sawa, T., Matsumura, Y., and Hori, K., 2000, Tumor vascular permeability and EPR effect in macromolecular therapeutics: a review. J. Control. Release 65: 271–284.
Maeda, H., 2001, The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Advan. Enzyme Regul. 41: 189–207.
Duncan, R., Seymour, L.W., O’Hare, K.B., Flanagan, P.A., Wedge, S., Hume, I.C., Ulbrich, K., Strohalm, J., Subr, V., Spareafico, F., Grandi, M., Ripamonti, M., Farao, M., and Suarato, A., 1992, Preclinical evaluation of polymer-bound doxorubicin. J. Control. Release 19: 331–346.
Vasey, P.A., Twelves, C., Kaye, S.B., Wilson, P., Morrison, R., Duncan, R., Thomson, A., Murray, L., Hilditch, T.E., Murray, T., Burtles, S., Frigerio, E., Fraier, D., and Cassidy, J., 1998, Phase I clinical and pharmacokinetic study of PK1. Abstructs of 3rd International Symposium on Polymer Therapeutics, p. 21.
Inoue, K., Okuno, S., Hamana, H., and Ito, T., 1993, Glyco-technology and DDS. FARUMASHIA 29: 1256–1260.
Nogusa, H., Yano, T., Okuno, S., Hamana, H., and Inoue, K., 1995, Synthesis of carboxymethylpullulan-peptide-doxorubicin conjugates and their properties. Chem. Pharm. Bull. 43: 1931–1938.
Sugawara, S., Okuno, S., Yano, T., Hamana, H., and Inoue, K., 2001, Characteristics of tissue distribution of various polysaccharides as drug carriers: influences of molecular weight and anionic charge on tumor targeting. Biol. Pharm. Bull. 24: 535–543.
Goldstein, I.J., Hay, G.W., Lewis, A., and Smith, F., 1965, Controlled degradation of polysaccharides by periodate oxidation, reduction, and hydrolysis. Methods in Carbohydr. Chem. 5: 361–370.
Kumazawa, E., and Tohgo, A., 1998, Antitumor activity of DX-8951f: a new camptothecin derivative. Exp. Opin. Invest. Drugs. 7: 625–632.
Kumazawa, E., Ochi, Y., Tanaka, N., Kajimura, T., and Inoue, K., 2001, A novel macromolecular carrier system for the camptothecin analog DX-8951f [I]: its antitumor activities in the murine Meth A solid tumor model. Proc. Am. Assoc. for Cancer Res. 42: 139.
Ochi, Y., Kumazawa, E., Nakata, M., Tanaka, N., and Inoue, K., 2001, A novel macromolecular carrier system for the camptothecin analog DX-8951f [II]: its antitumor activities in several model systems of human and murine tumors. Proc. Am. Assoc. for Cancer Res. 42: 376.
Masubuchi, N., Gohda, R., Seki, H., Hayashi, K., Atsumi, R., and Inoue, K., 2001, A novel macromolecular carrier system for the camptothecin analog DX-8951f [III]: pharmacokinetic evaluation in normal and tumor-bearing mice. Proc. Am. Assoc. for Cancer Res. 42: 376.
Soepenberg, O., De Jonge, M.J.A., Loos, W.J., Sparreboom, A., Eskens, F.A.L.M., De Heus, G., Elliott, S., Cheverton, P., Bastien, L., and Verweij, J., 2002, Phase I and pharmacologic study of the macromolecular topoisomerase-I-inhibitor DE-310 given once every 2 or 6 weeks in patients with solid tumors. Eur. J. Cancer (Suppl. 7) 38: S45.
Takimoto, C.H., Forero, F., Schwartz, G.H., Tolcher, A.W., Hammond, L.A., Patnaik, A., Ducharme, M., Cooke, B., De Jager, R., and Rowinsky, E.K., 2002, A phase I and pharmacokinetic study of DE-310 administered as a 3 hour infusion every 4 weeks (wks) to patients (pts) with advanced solid tumors or lymphomas. Eur. J. Cancer (Suppl. 7) 38: S46.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Kluwer Academic Publishers
About this chapter
Cite this chapter
Inoue, K., Kumazawa, E., Kuga, H., Susaki, H., Masubuchi, N., Kajimura, T. (2004). CM-Dextran-Polyalcohol-Camptothecin 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_9
Download citation
DOI: https://doi.org/10.1007/0-306-47932-X_9
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-47471-2
Online ISBN: 978-0-306-47932-8
eBook Packages: Springer Book Archive