FDA Approves Doxorubicin HCl Liposome Injection (DOXILR) in Combination With Bortezomib in Patients With Multiple Myeoma

The following is a message from the FDA's Office of Oncology Drug Products Director, Dr. Richard Pazdur:

On May 17, 2007, the U.S. Food and Drug Administration granted approval to doxorubicin HCl liposome injection (DOXIL®, Alza Corporation) for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Efficacy and safety were demonstrated in a randomized, multi-center, international study comparing the combination of DOXIL® plus bortezomib versus bortezomib alone in patients with multiple myeloma who have not previously received bortezomib and had received at least one prior therapy. DOXIL®, 30 mg/m2, was administered as a one-hour intravenous infusion on day four following bortezomib, 1.3 mg/m2, administered on days one, four, eight, and 11 in both treatment arms every 21 days. Data were evaluated from 646 randomized patients. The primary endpoint of time-to-progression (TTP-defined as time from randomization to progression or to death due to progression) was evaluated in a pre-specified interim analysis. Median TTP was 9.3 months in the combination arm compared to 6.5 months with bortezomib alone (HR=0.55; 95 percent CI [0.43, 0.71]; p < 0.0001). Survival data are immature at this time.

Safety data were evaluated from 636 treated patients (318 in each treatment arm). Grade 3/4 reactions reported in greater than or equal to 10 percent of patients and in a greater proportion of patients treated with the combination of DOXIL® and bortezomib included neutropenia and thrombocytopenia. Additional all-grade reactions reported in greater frequency with the combination arm included anemia, fatigue, pyrexia, nausea, vomiting, diarrhea, mucositis/stomatitis and hand foot syndrome.

The incidence of heart failure events was similar in the two treatment arms (3 percent in both groups).  Left ventricular ejection fraction decreases were observed in 13 percent of patients in the combination arm and in 8 percent of patients treated with bortezomib alone.

The initial rate of infusion of DOXIL® should be 1 mg/min to help minimize the risk of infusion reactions. Full prescribing information including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2007/050718s029lbl.pdf.