Clinical efficacy for refractory or intolerant AIDS-related Kaposi’s Sarcoma1

In an open-label, single-arm, multicenter study in patients retrospectively identified as having disease progression on prior systemic combination chemotherapy or as being intolerant to such therapy (n=77), DOXIL® demonstrated clinical efficacy and tolerability. Of the 77 patients, 34 were evaluable for investigator assessment and 42 were evaluable for indicator lesion assessment. The responses are shown below.1

Two analyses of tumor response were used: one based on investigator assessment of changes in lesions based on modified ACTG criteria (partial response defined as no new lesions, sites of disease, or worsening edema; flattening of ≥50% of previously raised lesions or area of indicator lesions decreasing by ≥50%; and response lasting at least 21 days with no prior progression), and one based on changes in up to 5 prospectively identified representative indicator lesions (partial response defined as flattening of ≥50% of previously raised indicator lesions, or >50% decrease in the area of indicator lesions and lasting at least 21 days with no prior progression).1


Study design1

DOXIL® was studied in an open-label, single-arm, multicenter study at a dose of 20 mg/m2 every 3 weeks, until disease progression or unacceptable toxicity.

Data are described for a cohort of 77 patients retrospectively identified as having disease progression on prior systemic combination chemotherapy (at least 2 cycles of a regimen containing at least 2 of 3 treatments: bleomycin, vincristine or vinblastine, or doxorubicin) or as being intolerant to such therapy. Of the 77 patients, 49 (64%) had received prior doxorubicin HCl.

The median time on study was 5.1 months (range, 1 day-15 months). The median cumulative dose of DOXIL® was 154 mg/m2 (range, 20-620 mg/m2).


Baseline patient characteristics1

Baseline characteristics were balanced, with the majority of patients classified as ACTG poor risk.



Response in patients with refractory or intolerant AIDS-related Kaposi's Sarcoma*1

*Patients with disease that progressed on prior combination chemotherapy or who were intolerant to such therapy.

There were no complete responses in this population.


Durable responses were also demonstrated in separate retrospective efficacy analyses of 2 trials1

  • The studies included subsets of patients who received single-agent DOXIL® and were on stable antiretroviral therapy for at least 60 days prior to enrollment and until a response was demonstrated1
    • 40% of patients in the first trial (7 of 17) had a durable response longer than 11.6 months (median duration was not reached)
    • 40% of patients in the second trial (4 of 11) also demonstrated a durable response

References

  1. DOXIL® (doxorubicin HCl liposome injection) Prescribing Information. Janssen Products, LP, Horsham, PA.

  

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): HFS may occur during therapy with DOXIL®. Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL® may be required.

  • HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): HFS may occur during therapy with DOXIL®. Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL® may be required.

  • HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Please see full Prescribing Information, including BOXED WARNINGS, for DOXIL® at www.DOXIL.com.

020669-150414