Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 5, pp 699–705

Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors

Authors

  • Jeffrey R. Infante
    • Sarah Cannon Research Institute
  • Vicki L. Keedy
    • Vanderbilt University
    • Sarah Cannon Research Institute
  • William C. Zamboni
    • UNC Lineberger Comprehensive Cancer Center, UNC Eshelman School of Pharmacy, Carolina Center for Cancer Nanotechnology Excellence, UNC Institute for Pharmacogenomics and Individualized TherapyThe University of North Carolina
  • Emily Chan
    • Vanderbilt University
  • Johanna C. Bendell
    • Sarah Cannon Research Institute
  • Wooin Lee
    • University of Kentucky
  • Huali Wu
    • UNC Lineberger Comprehensive Cancer Center, UNC Eshelman School of Pharmacy, Carolina Center for Cancer Nanotechnology Excellence, UNC Institute for Pharmacogenomics and Individualized TherapyThe University of North Carolina
  • Satoshi Ikeda
    • Yakult Honsha, Co., Ltd.
  • Hiroshi Kodaira
    • Yakult Honsha, Co., Ltd.
  • Mace L. Rothenberg
    • Vanderbilt University
  • Howard A. Burris III
    • Sarah Cannon Research Institute
Original Article

DOI: 10.1007/s00280-012-1960-5

Cite this article as:
Infante, J.R., Keedy, V.L., Jones, S.F. et al. Cancer Chemother Pharmacol (2012) 70: 699. doi:10.1007/s00280-012-1960-5

Abstract

Purpose

IHL-305 is a novel PEGylated liposome containing irinotecan. This study examined the safety profile and pharmacokinetics of IHL-305 and established the maximum tolerated dose and recommended phase II dose (RP2D).

Patients and methods

In a standard 3 + 3 design, IHL-305 was administered IV on day 1 of a 28-day treatment schedule. Subsequently, a 14-day treatment schedule was also explored. Two patient populations were evaluated separately: Patients with at least one wild-type (wt) allele of UGT1A1 (UDP glucoronosyltransferase 1A1) wt/wt or wt/*28 as one group (referred to as UGT1A1 wt group) and patients with UGT1A1*28 homozygous variant (*28/*28) as another group.

Results

Sixty patients were treated: 42 on the 28-day schedule and 18 on the 14-day schedule. Seven patients were homozygous variant (*28/*28). In the UGT1A1 wt group, the MTD and RP2D of IHL-305 was 160 mg/m2 every 28 days and 80 mg/m2 every 14 days. DLTs included nausea, vomiting, diarrhea, and neutropenia. The most common adverse events were nausea (75 %), vomiting (52 %), diarrhea (62 %), anorexia (57 %), and fatigue (57 %). At the MTD for both schedules, IHL-305 administration resulted in a high and prolonged exposure of sum total irinotecan, released irinotecan, and SN-38 in plasma. One partial response was observed in a patient with breast cancer and eight patients had stable disease for >6 months.

Conclusions

IHL-305, a novel preparation of irinotecan encapsulated in liposomes, can be safely given to patients in a repeated fashion on a 4- or 2-week dosing schedule.

Keywords

PEGylated liposomal irinotecanIHL-305Phase IPharmacokinetic

Copyright information

© Springer-Verlag 2012