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 < 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.
|Original language||English (US)|
|Number of pages||5|
|Journal||Cancer Treatment Reports|
|State||Published - Jan 1 1981|
ASJC Scopus subject areas
- Cancer Research