This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ramsay, E. C. Articles by Bally, M. B. PubMed PubMed Citation Articles by Ramsay, E. C. Articles by Bally, M. B.

Irinophore C: A Liposome Formulation of Irinotecan with Substantially Improved Therapeutic Efficacy against a Panel of Human Xenograft Tumors

Authors' Affiliations: ¹ Department of Advanced Therapeutics, BC Cancer Agency; ² Department of Pathology and Laboratory Medicine and ³ Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada; and ⁴ School of Pharmacy, University of Tasmania, Hobart, Tasmania, Australia

Requests for reprints: Marcel Bally, Department of Advanced Therapeutics, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3. Phone: 604-675-8020; Fax: 604-675-8183; E-mail: mbally{at}bccrc.ca.

Purpose: To assess the pharmacokinetics, tumor drug accumulation, and therapeutic activity of Irinophore C, a novel liposomal formulation of irinotecan (CPT-11).

Experimental Design: The plasma lactone/carboxy levels of CPT-11 and SN-38 were determined in mice after a single i.v. dose of irinotecan (Camptosar), or Irinophore C, and the plasma t_1/2, plasma area under the curve, plasma C_max, and plasma clearance were calculated. Further, plasma and tumor drug levels were also measured in tumor-bearing mice following Irinophore C treatment. The efficacy of Irinophore C was compared with that of Camptosar in five s.c. human tumor xenografts using single-dose treatment (LS 180), a total of three doses administered at 4-day intervals (H460), or a total of three doses administered at 7-day intervals (Capan-1, PC-3, and HT-29).

Results: Compared with Camptosar, Irinophore C mediated an 8-fold increase in t_1/2, a 100-fold increase in C_max, a 1,000-fold increase in area under the curve, and a 1,000-fold decrease in clearance for the active lactone form of CPT-11. Further, the plasma and tumor SN-38 lactone levels were consistent for at least 48 h post-Irinophore C injection. Camptosar treatment (40 mg/kg) mediated a delay in the time required for tumors to increase to four times their pretreatment size compared with controls (T-C). T-Cs ranged from 2 days (LS 180 model) to 18 days (PC-3 model). Irinophore C (40 mg/kg) engendered T-Cs ranging from 14 days (LS 180 model) to 87 days (Capan-1 model).

Conclusion: Irinophore C improved CPT-11/SN-38 pharmacokinetics, promoted tumor drug accumulation, and increased therapeutic efficacy in a panel of five distinct human tumor xenografts.