Related Pages Multiple Myeloma/Other Plasma Cell Neoplasms 1 NCI's gateway for information about multiple myeloma and other plasma cell neoplasms. Drug Information Summaries 2 NCI's drug information summaries provide consumer-friendly information about certain drugs that are approved by the U.S. Food and Drug Administration (FDA) to treat cancer or conditions related to cancer.

Brand name(s): Doxil®

• Approved for multiple myeloma

Full prescribing information ³ is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On May 17, 2007, the U.S. Food and Drug Administration (FDA) granted approval to doxorubicin HCl liposome injection (Doxil®, Alza Corporation) for use in combination with bortezomib ⁴ 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, multicenter, international study comparing the combination of doxorubicin HCl liposome plus bortezomib versus bortezomib alone in patients with multiple myeloma who have not previously received bortezomib and had received at least one prior therapy.

Doxorubicin HCl liposome, 30 mg/m2, was administered as a one-hour intravenous infusion on day 4 following bortezomib, 1.3 mg/m2, administered on days 1, 4, 8 and 11 in both treatment arms every twenty-one 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% 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 doxorubicin HCl liposome and bortezomib included neutropenia and thrombocytopenia. Additional all-grade reactions reported in greater frequency with the combination arm included anemia, fatigue, pyrexia (fever), 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 doxorubicin HCl liposome should be 1 mg/min to help minimize the risk of infusion reactions.

Glossary Terms

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

A statistics term. The middle value in a set of measurements.

A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth.

A condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell).

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A condition in which there is a lower-than-normal number of platelets in the blood. It may result in easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues.