Phase I investigation of ametantrone.
Ametantrone is the third of a family of anthracene derivatives to undergo a phase I trial in man. Sixteen patients received 33 courses of drug as a single iv dose given every 3 weeks. Escalations proceeded from 120 to 180 mg/m2. Predictable and reversible leukopenia was the dose-limiting toxic effect. Four patients developed thrombocytopenia. Nonhematologic toxic effects included a marked cumulative blue discoloration of the skin seen in all patients receiving more than three courses of the drug. This cumulative cosmetic effect may also be dose-limiting. Other nonhematologic toxic effects included: blue urine (all patients), nausea (two), vomiting (one), a blue stool (one), and reversible elevations of either SGOT or alkaline phosphatase (two). No objective responses were seen in this study. A dose of 140-160 mg/m2 is recommended as the starting dose for phase II trials in patients who have received prior chemotherapy or radiotherapy.
D000368:Aged; D000880:Anthraquinones / Q000008:administration & dosage* / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001853:Bone Marrow / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000031:analogs & derivatives*; D009369:Neoplasms / Q000188:drug therapy*; D012871:Skin Diseases / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
D000880:Anthraquinones; D008942:Mitoxantrone; C020182:ametantrone