Liposomal daunorubicin: In vitro and in vivo efficacy in multiple myeloma

Liposomal encapsulation of anthracyclines is a potential method of drug tar geting, altering both the antitumour activity and side-effect profile of an thracyclines. Liposomal daunorubicin (daunoxome) shows both altered pharmac okinetics and a potential for reducing dose-limiting cardiotoxicity compare d to conventional daunorubicin. Anthracyclines have a common role in the tr eatment of multiple myeloma, a prevalent and fatal haematological malignanc y. Avoiding cumulative anthracycline toxicity in these patients is importan t. There is also a need for more effective relapse schedules given that man y patients have chemosensitive disease at relapse. We have analysed daunoxo me in vitro in myeloma cell lines using a thymidine-based cytotoxicity assa y and show superior efficacy compared to a pegylated liposomal doxorubicin derivative. Subsequently we have treated seven relapsed myeloma patients wi th a regime consisting of oral CCNU 25-50 mg/m(2) on day 1, 4 days of oral dexamethasone 10 mg/m(2) and intravenous daunoxome (liposomal daunorubicin) given for 4 days (total 100 mg/m(2)). The main toxicity was myelosuppressi on but non-haematological toxicity was minimal and the regime was well tole rated. Four out of seven of these heavily pretreated patients responded. To gether with the in vitro data on its cytotoxicity in myeloma and its favour able pharmacokinetic profile further studies of liposomal daunorubicin in m yeloma would be warranted. Copyright (C) 1998 John Wiley & Sons, Ltd.