Phase I trial of ICRF-187 by 48-hour continuous infusion

Cancer Treat Rep. May-Jun 1981;65(5-6):459-63.


ICRF-187 is the D-enantiomer of the racemic antitumor agent ICRF-159 and was selected for clinical trials on the basis of aqueous solubility suitable for iv administration. Eighteen patients with refractory advanced solid tumors received ICRF-187 by a 48-hour continuous iv infusion in 5% Dextrose in Water, USP. The total dose ranged from 200 to 1000 mg/m2/48 hours. Courses were repeated at 22--28-day intervals. The major toxic effect was reversible granulocytopenia, with the nadir on Day 12 and the recovery by Day 22. At a dose of 1000 mg/m2/48 hours, the median nadir total wbc count was 1700/mm3 (range, 1300--2600), and the median nadir granulocyte count was 597/mm3 (range, 270--1300). Platelet count nadirs of less than 100,000/mm3 occurred in only three of 16 courses at this level. Granulocyte toxicity was not cumulative and was less severe in repeated courses (median nadir, 1000/mm3 in courses two and three). Mild nausea, malaise, and three instances of alopecia were the only nonhematologic toxic effects encountered. Compared to other schedules, a continuous 48-hour infusion of ICRF-187 seems to have greater toxic effects for a given total dose, and this may predict greater biologic effect. A starting dose of 1000 mg/m2 by a 48-hour continuous infusion is recommended for phase II trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Granulocytes
  • Humans
  • Infusions, Parenteral
  • Leukocyte Count
  • Leukopenia / chemically induced
  • Neoplasms / drug therapy*
  • Piperazines / administration & dosage*
  • Platelet Count
  • Razoxane / administration & dosage*
  • Razoxane / adverse effects
  • Stereoisomerism
  • Thrombocytopenia / chemically induced


  • Piperazines
  • Razoxane