Phase I study of liposomal annamycin

Annamycin is a highly lipophilic anthracycline with the ability to bypass t he MDR-1 mechanism of cellular drug resistance. In this phase I study, anna mycin entrapped in liposomes was administered by a 1- to 2-h intravenous in fusion at 3-week intervals. Thirty-six patients with relapsed solid tumors were treated and 109 courses were administered at doses ranging from 3 to 2 40 mg/m(2). The dose-limiting toxicity was thrombocytopenia. Five patients had a probable allergic reaction, requiring discontinuation of treatment in one. Treatment was well tolerated otherwise. No cardiac toxicity was seen on endomyocardial biopsy of four patients studied. There was limited gastro intestinal toxicity and no alopecia. No objective tumor responses were obse rved. Pharmacokinetic studies at 24, 120 and 240 mg/m(2) showed a biexponen tial plasma concentration-versus-time profile. There was a linear relations hip between the dose and the maximal plasma concentration with relatively c onstant plasma clearance values. The maximum tolerated dose (MTD) for lipos omal annamycin defined in this study is 210 mg/m(2). Because of a subsequen t change in the formulation of the drug, future studies will use 190 mg/m(2 ) as the MTD.