Doxil (doxorubicin hydrochloride liposome injection) - 3 indications

Scroll down for additional information on each indication:

• Ovarian cancer
• AIDS-related Kaposi’s Sarcoma
• Multiple myeloma

General Information

Doxil liposomal infusion is an anthracycline topoisomerase inhibitor.

Doxil is specifically indicated for:

• the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy;
• AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy;
• in combination with bortezomib, for patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy

Doxil is supplied as a liposomal infusion for intravenous administration. Scroll down for the recommended dose for each indication.

Mechanism of Action

Doxil is a liposomal formulation of doxorubicin, an intravenous chemotherapy agent. Doxil uses a novel, targeted delivery system called STEALTH technology to help evade recognition and uptake by the immune system. Unlike conventional liposomes, STEALTH liposomes evade detection and destruction by the immune system so they can circulate in the body longer. A long circulation time increases the likelihood that the liposomes and their pharmaceutical contents will reach their targeted tumor site.

Side Effects

Adverse effects associated with the use of Doxil may include, but are not limited to, the following:

• asthenia
• fatigue
• fever
• anorexia
• nausea
• vomiting
• stomatitis
• diarrhea
• constipation
• hand-foot syndrome
• rash
• neutropenia
• thrombocytopenia
• anemia

The Doxil drug label comes with the following Black Box Warning: Doxil can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450 mg/m2 to 550 mg/m2 . Assess left ventricular cardiac function prior to initiation of Doxil liposomal infusion and during and after treatment. Serious, life-threatening, and fatal infusion-related reactions can occur with Doxil liposomal infusion. Acute infusion-related reactions occurred in 11% of patients with solid tumors. Withhold Doxil liposomal infusion for infusion-related reactions and resume at a reduced rate. Discontinue for serious or life threatening infusion-related reactions. 

Indication 1 - patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy

Dosing/Administration

The recommended dose of Doxil liposomal infusion is 50 mg/m2 intravenously over 60 minutes every 28 days until disease progression or unacceptable toxicity.

Clinical Trial Results

Studies evaluating Doxil included three Phase II trials conducted among women with relapsed or refractory ovarian cancer, as well as preliminary results of a Phase III randomized trial. Patients in the Phase II studies with refractory ovarian cancer demonstrated a 13.8 percent response rate, defined as a reduction in tumor size of at least 50%. This response rate was supported by interim analysis of Phase III data.

Indication 2 - AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy

Dosing/Administration

The recommended dose is 20 mg/m2 intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity.

Clinical Trial Results

An open-label, single-arm, multicenter study evaluated Doxil at a dose of 20 mg/m2 every 3 weeks, until disease progression or unacceptable toxicity. Data is described for a cohort of 77 patients retrospectively identified as having disease progression on prior systemic combination chemotherapy or as being intolerant to such therapy. Response rate was: Partial (PR) 27%; Stable disease: 29% and Progression: 44%.

Indication 3 - in combination with bortezomib, for previously treated patients with multiple myeloma who have not previously received bortezomib 

Dosing/Administration

The recommended dose of Doxil liposomal infusion is 30 mg/m2 intravenously over 60 minutes on day 4 of each 21-day cycle for eight cycles or until disease progression or unacceptable toxicity. Administer Doxil liposomal infusion after bortezomib on day 4 of each cycle.

Clinical Trial Results

The efficacy of Doxil liposomal infusion in combination with bortezomib was evaluated in a randomized, open-label, international, multicenter study in 646 patients who had not previously received bortezomib and whose disease progressed during or after at least one prior therapy. Patients were randomized (1:1) to receive either Doxil liposomal infusion (30 mg/m2 ) administered IV on day 4 following bortezomib or bortezomib alone every 3 weeks for up to 8 cycles or until disease progression or unacceptable toxicity. Data showed a significant outcome on the primary measure of time to progression (TTP) for the combination.