Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models

  • Authors:
    • Takeshi Matsuzaki
    • Akimitsu Takagi
    • Tomio Furuta
    • Satoshi Ueno
    • Akinobu Kurita
    • Gou Nohara
    • Hiroshi Kodaira
    • Seigo Sawada
    • Shusuke Hashimoto
  • View Affiliations

  • Published online on: September 20, 2011     https://doi.org/10.3892/or.2011.1465
  • Pages: 189-197
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Abstract

The antitumor effect of IHL-305, a novel pegylated liposome containing irinotecan, was investigated in human xenograft models. After subcutaneous transplantation of several human cancer cell lines (colorectal, non-small cell lung, small cell lung, prostate, ovarian and gastric cancer cells) to nude mice, IHL-305 or CPT-11 was administered intravenously 3 times at 4-day intervals. In all xenograft models tested, IHL-305 showed superior antitumor activity to that of CPT‑11 and a comparable tumor-growth-inhibitory effect at one-eighth or less of the dose of CPT-11, even against HT-29 colorectal and NCI-H460 non-small cell lung cancer cell lines, which show intrinsic resistance to CPT-11. A single injection or 2 injections of IHL-305 on several dosing schedules also resulted in a significant antitumor effect compared to that of vehicle control in a dose-dependent manner and showed comparable antitumor activity at about one-fifth the dose of the maximum tolerated dose of CPT-11. The analysis of the concentrations of irinotecan and SN-38, an active metabolite of CPT-11, in plasma and tumors revealed that irinotecan was maintained at high concentrations, and the prolonged presence of SN-38 in plasma and tumors in IHL-305 treated mice compared with CPT-11-treated mice. Therefore, the stronger tumor inhibitory effect of IHL-305, as compared to CPT-11, was associated with the difference in the concentration of irinotecan in plasma or tumors after each agent was administered and with the maintainance of a higher concentration of SN-38. These results indicate that IHL-305 demonstrated superior antitumor activity against a wide range of tumors at lower doses than CPT-11.

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January 2012
Volume 27 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Matsuzaki T, Takagi A, Furuta T, Ueno S, Kurita A, Nohara G, Kodaira H, Sawada S and Hashimoto S: Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models. Oncol Rep 27: 189-197, 2012.
APA
Matsuzaki, T., Takagi, A., Furuta, T., Ueno, S., Kurita, A., Nohara, G. ... Hashimoto, S. (2012). Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models. Oncology Reports, 27, 189-197. https://doi.org/10.3892/or.2011.1465
MLA
Matsuzaki, T., Takagi, A., Furuta, T., Ueno, S., Kurita, A., Nohara, G., Kodaira, H., Sawada, S., Hashimoto, S."Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models". Oncology Reports 27.1 (2012): 189-197.
Chicago
Matsuzaki, T., Takagi, A., Furuta, T., Ueno, S., Kurita, A., Nohara, G., Kodaira, H., Sawada, S., Hashimoto, S."Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models". Oncology Reports 27, no. 1 (2012): 189-197. https://doi.org/10.3892/or.2011.1465