Select therapeutic use:

Gynecologic Cancers:

Kaposi's sarcoma:

Indications for: DOXIL

AIDS-related Kaposi's sarcoma refractory or intolerance to prior systemic chemotherapy.

Clinical Trials:

AIDS-Related Kaposi’s Sarcoma

Doxorubicin hydrochloride liposome injection was studied in an open-label, single-arm, multicenter study at a dose of 20mg/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 (at least two cycles of a regimen containing at least 2 of 3 treatments: bleomycin, vincristine or vinblastine, or doxorubicin) or as being intolerant to such therapy. Forty-nine of the 77 (64%) patients had received prior doxorubicin hydrochloride. 

Of the 77 patients with refractory AIDS-related Kaposi’s Sarcoma, 34 were evaluable for investigator assessment and 42 were evaluable for indicator lesion assessment. In the investigatory assessment, the following results were observed among all evaluable patients (n=34) and evaluable patients who received prior doxorubicin (n=20), respectively:

  • Response (no complete responses in this population)

    • Partial (PR): 27% vs 30%

    • Stable: 29% vs 40%

    • Progression: 44% vs 30%

  • Duration of PR (Days)

    • Median: 73 vs 89

    • Range: 42+ to 210+ vs 42+ to 210+

  • Time to PR (Days)

    • Median: 43 vs 53

    • Range: 15 – 133 vs 15 – 109

In the indicator lesion assessment, the following results were observed among all evaluable patients (n=42) and evaluable patients who received prior doxorubicin (n=23), respectively:

  • Response (no complete responses in this population)

    • Partial (PR): 48% vs 52%

    • Stable: 26% vs 30%

    • Progression: 26% vs 17%

  • Duration of PR (Days)

    • Median: 71 vs 79

    • Range: 22+ to 210+ vs 35 to 210+

  • Time to PR (Days)

    • Median: 22 vs 48

    • Range: 15 – 109 vs 15 – 109

Retrospective efficacy analyses were performed in two trials that had subsets of patients who received single-agent doxorubicin hydrochloride liposome injection and who were on stable antiretroviral therapy for at least 60 days prior to enrollment and until a response was demonstrated. In one trial, 7 of 17 (40%) patients had a durable response (median duration not reached but was longer than 11.6 months). In the second trial, 4 of 11 patients (40%) on a stable antiretroviral therapy demonstrated durable responses.

Adult Dosage:

Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 20mg/m2 once every 3 weeks until disease progression or unacceptable toxicity. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling.

Children Dosage:

Not established.

Boxed Warning:

Cardiomyopathy. Infusion-related reactions.

DOXIL Warnings/Precautions:

Not substitutable on a mg/mg basis with other doxorubicin products. Risk of cardiomyopathy (including left ventricular failure), acute infusion-related reactions. History of cardiovascular disease. Have medications to treat infusion-related reactions and resuscitative equipment available. Discontinue if serious infusion-related reactions occur. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (eg, MUGA, ECG). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Hepatic impairment. Embryo-fetal toxicity. Advise females and males of reproductive potential to use effective contraception during and for 6 months after last dose. Pregnancy: avoid during 1st trimester. Nursing mothers: not recommended.

DOXIL Classification:

Anthracycline.

DOXIL Interactions:

Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity.

Adverse Reactions:

Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange).

Drug Elimination:

Hepatic.

Generic Drug Availability:

YES

How Supplied:

Single-dose vials (10mL, 25mL)—1

Leukemias, lymphomas, and other hematologic cancers:

Indications for: DOXIL

Multiple myeloma, in combination with bortezomib, in patients not previously treated with bortezomib and who have received at least one prior therapy.

Clinical Trials:

Multiple Myeloma

The efficacy of doxorubicin hydrochloride liposome injection in combination with bortezomib was evaluated in Trial 6, 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 doxorubicin hydrochloride liposome injection (30 mg/m2) administered IV on day 4 following bortezomib (1.3 mg/m2 IV on days 1, 4, 8 and 11) or bortezomib alone every 3 weeks for up to 8 cycles or until disease progression or unacceptable toxicity.

The primary outcome measure was time to progression (TTP). TTP was defined as the time from randomization to the first occurrence of progressive disease or death due to progressive disease.

Results showed that treatment with doxorubicin hydrochloride liposome injection plus bortezomib achieved a significant improvement in TTP compared with bortezomib alone (HR, 0.55; 95% CI, 0.43-0.71; P <.001). There were 99 patients in the combination arm who had disease progression or death due to progression compared with 150 patients in the bortezomib alone arm. The median duration of response was 10.2 months (95% CI, 10.2-12.9) for the combination arm and 7 months (95% CI, 5.9-8.3) for the bortezomib alone arm.

At the final analysis of survival, 78% of subjects in the doxorubicin hydrochloride liposome injection and bortezomib combination therapy group and 80% of subjects in the bortezomib monotherapy group had died after a median follow up of 8.6 years. The median survival was 33 months in the doxorubicin hydrochloride liposome injection and bortezomib combination therapy group and 31 months in the bortezomib monotherapy group. There was no difference observed in  overall survival at the final analysis

Adult Dosage:

Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 30mg/m2 on day 4 of each cycle following bortezomib (see full labeling for bortezomib dose) for 8 cycles or until disease progression or unacceptable toxicity. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling.

Children Dosage:

Not established.

Boxed Warning:

Cardiomyopathy. Infusion-related reactions.

DOXIL Warnings/Precautions:

Not substitutable on a mg/mg basis with other doxorubicin products. Risk of cardiomyopathy (including left ventricular failure), acute infusion-related reactions. History of cardiovascular disease. Have medications to treat infusion-related reactions and resuscitative equipment available. Discontinue if serious infusion-related reactions occur. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (eg, MUGA, ECG). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Hepatic impairment. Embryo-fetal toxicity. Advise females and males of reproductive potential to use effective contraception during and for 6 months after last dose. Pregnancy: avoid during 1st trimester. Nursing mothers: not recommended.

DOXIL Classification:

Anthracycline.

DOXIL Interactions:

Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity.

Adverse Reactions:

Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange).

Drug Elimination:

Hepatic.

Generic Drug Availability:

YES

How Supplied:

Single-dose vials (10mL, 25mL)—1