PHASE-I STUDY OF A 5-DAY SCHEDULE OF MITOXANTRONE (DIHYDROXYANTHRACENEDIONE)

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (6) , 1303-1306
Abstract
Mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]-amino]-9,10-anthracenedione dihydrochloride) in animal studies appears to have a mechanism of action and broad antitumor spectrum similar to the anthracyclines and in preliminary animal studies is without cardiotoxicity. To determine the maximally tolerated dose, mitoxantrone was given to 25 patients with various advanced solid tumors. Sixteen patients had received prior doxorubicin and/or lomustine (CCNU). Myelosuppression was the major toxic effect. All 3 patients who received mitoxantrone doses .gtoreq. 2.73 mg/m2 .times. 5 days experienced moderate (2000-3000 cells/mm3) or severe (< 2000 cells/mm3) leukopenia. Thrombocytopenia was also encountered in 3 of these 13 patients (severe in 1, < 50,000 cells/mm3). At dose levels < 2.73 mg/m2 .times. 5 days, myelosuppression was seen in 4 of 12 patients (3 with milk leukopenia and 1 with mild thrombocytopenia). The blood cell count nadir occurred in 10 days; full recovery occurred by Day 21. Minor clinically insignificant ECG changes occurred in 5 patients. Minor and transient antitumor effects were seen in 5 patients. The maximum tolerated dose of mitoxantrone over a 5-day course is 2.73 mg/m2, with leukopenia being the limiting toxic effect.

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