PHASE-I AND PHARMACOLOGICAL STUDY OF LIPOSOMAL DAUNORUBICIN (DAUNOXOME)

We have completed a phase I and pharmacology study of liposomally-enca psulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were eva luable. No toxicity was encountered at the initial dose-escalation ste ps from 10 to 60 mg/m(2). At 80 mg/m(2), two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m(2). Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor object ive response was observed in this population of refractory solid tumor s. Pharmacokinetics differed from those of the free drug with no detec tion of daunorubicinol. We recommend future phase II studies with a do se of 100 mg/m(2) in previously treated and 120 mg/m(2) of DaunoXome i n previously untreated patients with solid tumors.