title: Antitumor activity of IHL-305, a novel pegylated liposome containing             irinotecan, in human xenograft models.
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.
authors.affiliation: Yakult Central Institute for Microbiological Research, Pharmaceutical Development Department, Yakult Honsha Co., Ltd., 1796 Yaho, Tokyo 186-8650, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Takagi
authors.forename: Tomio
authors.initials: T
authors.lastname: Furuta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kurita
authors.forename: Gou
authors.initials: G
authors.lastname: Nohara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kodaira
authors.forename: Seigo
authors.initials: S
authors.lastname: Sawada
authors.forename: Shusuke
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D006801:Humans; D000077146:Irinotecan; D008081:Liposomes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011092:Polyethylene Glycols; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin