Schedule dependence of activity of the amsacrine analogue CI-921 towards P388 leukaemia and Lewis lung carcinoma

Abstract

The 4-methyl-5-(N-methyl)carboxamide derivative (CI-921; NSC 343499) of the clinical antileukaemia agent amsacrine is highly active towards P388 leukaemia and Lewis lung carcinoma in mice. When administered intraperitoneally at the optimal schedule and dose, CI-921 provided 5/650-day survivors in leukaemic mice and 10/11 60-day survivors in mice previously inoculated intravenously with Lewis lung cells. An intermittent (every 4 days X 3) schedule was superior to single dose, daily X 5 or daily X 9 schedules. Although intraperitoneal dosage was superior to intravenous or oral dosage for the treatment of intraperitoneally inoculated P388 leukaemia, all three routes of administration provided similar results with intravenously inoculated Lewis lung or subcutaneously implanted P388 cells. Daily intraperitoneal dosage schedules provided sharper dose-response relationships than intermittent schedules, and with daily schedules 1.5-fold rather than 2-fold dose increments were necessary for reliable detection of activity against Lewis lung carcinoma.