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CPT-11: clinical experience in phase I studies

J P Armand1

  • 1Institut Gustave Roussy, Villejuif, France.

Seminars in Oncology
|February 1, 1996
PubMed
Summary

Phase I studies of CPT-11 (irinotecan) established dose-limiting toxicities of diarrhea and neutropenia. Different intravenous schedules were evaluated across Europe, the US, and Japan to determine optimal dosing for Phase II trials.

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Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Cancer Therapeutics

Background:

  • Phase I clinical trials investigated CPT-11 (irinotecan) to establish safe and effective dosing regimens.
  • Diarrhea and neutropenia were identified as the primary dose-limiting toxicities across international studies.

Purpose of the Study:

  • To determine the maximum tolerated dose (MTD) and optimal intravenous administration schedule for CPT-11.
  • To inform the design of subsequent Phase II investigations for CPT-11 efficacy.

Main Methods:

  • Conducted Phase I studies in Europe, the United States, and Japan.
  • Evaluated various intravenous infusion schedules, including once every 3 weeks and weekly regimens.
  • Assessed dose-limiting toxicities and determined MTD for each schedule.

Main Results:

  • MTD varied by schedule and region: 240-250 mg/m2 (3-weekly) and 100-150 mg/m2 (weekly) in Japan/US.
  • European studies identified MTDs of 90-100 mg/m2/day (3-day infusion) and 100-115 mg/m2 (weekly).
  • A 3-weekly single infusion of 350 mg/m2, with loperamide, was well-tolerated and convenient for outpatient use.

Conclusions:

  • The weekly intermittent schedule demonstrated higher dose intensity in US and Japanese trials.
  • European Phase II studies adopted a 3-weekly single infusion of 350 mg/m2, enhanced by loperamide, due to tolerability and convenience.

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