Background: Liposomal daunorubicin is an effective cytotoxic agent in patients with Kaposi sarcoma and hematologic malignancies. Anthracycline-based chemotherapy regimens, such as vincristine/doxorubicin/dexamethasone (VAD), are standard in the treatment of patients with multiple myeloma (MM). Cardiotoxicity remains a limiting factor in dose escalation of anthracyclines, and multidrug resistance (MDR) develops rapidly on exposure to anthracyclines. Liposomal daunorubicin was designed in an attempt to overcome MDR and to reduce anthracycline-related toxicities. Thus, an open-label, Phase II clinical study was conducted by the International Oncology Study Group to assess the efficacy and safety of intravenous liposomal daunorubicin at a dose of 100 mg/m2 given every 3 weeks for a maximum of 6 cycles in patients with recently diagnosed MM (n = 4 patients) or recurrent/refractory MM (n = 37 patients).
Methods: Liposomal daunorubicin was administered as a single agent for the initial two cycles of therapy, and dexamethasone was added to all subsequent cycles. The primary study end point was response rates. Thirty-eight patients were treated, 35 of whom were evaluable for response.
Results: A partial response was achieved in six patients (17%), including one patient with disease that previously was refractory to VAD therapy. Stable disease was observed in 22 patients (63%). The principal toxicity was myelosuppression. Grade 3 or 4 hematologic toxicities included granulocytopenia (26%), anemia (Grade 3 only; 11%), thrombocytopenia (11%), and febrile neutropenia (13%). The median survival in 35 patients with recurrent disease was 7.6 months.
Conclusions: Liposomal daunorubicin had activity in this population of poor-risk patients that was comparable to the activity of standard regimens. Further studies of this agent in combination with other anti-MM agents are warranted.