Doxil Drug Information
Generic name: DOXORUBICIN HYDROCHLORIDE
Uses of Doxil
Ovarian Cancer
DOXIL liposomal infusion is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.
AIDS-Related Kaposi’s Sarcoma
DOXIL liposomal infusion is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.
Multiple Myeloma
DOXIL liposomal infusion, 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.
Dosage & Administration of Doxil
Dose Modifications for Adverse Reactions
Do not increase DOXIL liposomal infusion after a dose reduction for toxicity. Table 1: Recommended Dose Modifications for Hand-Foot Syndrome, Table 2: Recommended Dose Modifications of DOXIL Liposomal Infusion for Toxicity When Administered in Combination With Bortezomib For neuropathic pain or peripheral neuropathy, no dosage adjustments are required for DOXIL liposomal infusion. Dilute doses exceeding 90 mg in 500 mL of 5% Dextrose Injection, USP prior to administration.
Refrigerate diluted DOXIL liposomal infusion at 2°C to 8°C (36°F to 46°F) and administer within 24 hours. Administration Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is present.
Do not use with in-line filters. Administer the first dose of DOXIL liposomal infusion at an initial rate of 1 mg/min. If no infusion-related adverse reactions are observed, increase the infusion rate to complete the administration of the drug over one hour.
Do not rapidly flush the infusion line. Do not mix DOXIL liposomal infusion with other drugs. Management of Suspected Extravasation Discontinue DOXIL liposomal infusion for burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation.
Manage confirmed or suspected extravasation as follows: • Do not remove the needle until attempts are made to aspirate extravasated fluid • Do not flush the line • Avoid applying pressure to the site • Apply ice to the site intermittently for 15 minute 4 times a day for 3 days • If the extravasation is in an extremity, elevate the extremity
Procedure for Proper Handling and Disposal
DOXIL liposomal infusion is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 If DOXIL liposomal infusion comes into contact with skin or mucosa, immediately wash thoroughly with soap and water.
| Toxicity | Dose Adjustment |
|---|---|
| Hand-Foot Syndrome (HFS) | |
| Grade 1: Mild erythema, swelling, or desquamation not interfering with daily activities | • If no previous Grade 3 or 4 HFS: no dose adjustment. • If previous Grade 3 or 4 HFS: delay dose up to 2 weeks, then decrease dose by 25%. |
| Grade 2: Erythema, desquamation, or swelling interfering with, but not precluding normal physical activities; small blisters or ulcerations less than 2 cm in diameter | • Delay dosing up to 2 weeks or until resolved to Grade 0–1. • Discontinue DOXIL liposomal infusion if no resolution after 2 weeks. • If resolved to Grade 0–1 within 2 weeks: • And no previous Grade 3 or 4 HFS: continue treatment at previous dose. • And previous Grade 3 or 4 toxicity: decrease dose by 25%. |
| Grade 3: Blistering, ulceration, or swelling interfering with walking or normal daily activities; cannot wear regular clothing | • Delay dosing up to 2 weeks or until resolved to Grade 0–1, then decrease dose by 25%. • Discontinue DOXIL liposomal infusion if no resolution after 2 weeks. |
| Grade 4: Diffuse or local process causing infectious complications, or a bed ridden state or hospitalization | • Delay dosing up to 2 weeks or until resolved to Grade 0–1, then decrease dose by 25%. • Discontinue DOXIL liposomal infusion if no resolution after 2 weeks. |
| Stomatitis | |
| Grade 1: Painless ulcers, erythema, or mild soreness | • If no previous Grade 3 or 4 toxicity: no dose adjustment. • If previous Grade 3 or 4 toxicity: delay up to 2 weeks then decrease dose by 25%. |
| Grade 2: Painful erythema, edema, or ulcers, but can eat | • Delay dosing up to 2 weeks or until resolved to Grade 0–1. • Discontinue DOXIL liposomal infusion if there is no resolution after 2 weeks. • If resolved to Grade 0–1 within 2 weeks: • And no previous Grade 3 or 4 stomatitis: resume treatment at previous dose. • And previous Grade 3 or 4 toxicity: decrease dose by 25%. |
| Grade 3: Painful erythema, edema, or ulcers, and cannot eat | • Delay dosing up to 2 weeks or until resolved to Grade 0–1. Decrease dose by 25% and return to original dose interval. • If after 2 weeks there is no resolution, discontinue DOXIL liposomal infusion. |
| Grade 4: Requires parenteral or enteral support | • Delay dosing up to 2 weeks or until resolved to Grade 0–1. Decrease dose by 25% and return to original dose interval. • If after 2 weeks there is no resolution, discontinue DOXIL liposomal infusion. |
| Neutropenia or Thrombocytopenia | |
| Grade 1 | No dose reduction |
| Grade 2 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume treatment at previous dose |
| Grade 3 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume treatment at previous dose |
| Grade 4 | Delay until ANC ≥ 1,500 and platelets ≥ 75,000; resume at 25% dose reduction or continue previous dose with prophylactic granulocyte growth factor |
| Toxicity | DOXIL Liposomal Infusion |
|---|---|
| Fever ≥38°C and ANC <1,000/mm 3 | • Withhold dose for this cycle if before Day 4; • Decrease dose by 25%, if after Day 4 of previous cycle. |
| On any day of drug administration after Day 1 of each cycle: • Platelet count <25,000/mm 3 • Hemoglobin <8 g/dL • ANC <500/mm 3 | • Withhold dose for this cycle if before Day 4; • Decrease dose by 25%, if after Day 4 of previous cycle AND if bortezomib is reduced for hematologic toxicity. |
| Grade 3 or 4 non-hematologic drug related toxicity | Do not dose until recovered to Grade <2, then reduce dose by 25%. |
Side Effects of Doxil
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates on other clinical trials and may not reflect the rates observed in clinical practice. The most common adverse reactions (>20%) observed with DOXIL liposomal infusion are asthenia, fatigue, fever, nausea, stomatitis, vomiting, diarrhea, constipation, anorexia, hand-foot syndrome, rash and neutropenia, thrombocytopenia and anemia. The following tables present adverse reactions from clinical trials of single-agent DOXIL liposomal infusion in ovarian cancer and AIDS-Related Kaposi’s sarcoma.
Patients With Ovarian Cancer The safety data described below are from Trial 4, which included 239 patients with ovarian cancer treated with DOXIL liposomal infusion 50 mg/m 2 once every 4 weeks for a minimum of four courses in a randomized, multicenter, open-label study. In this trial, patients received DOXIL liposomal infusion for a median number of 3.2 months (range 1 day to 25.8 months). Table 3 presents the hematologic adverse reactions from Trial 4.
Table 4: Non-Hematologic The following additional adverse reactions were observed in patients with ovarian cancer with doses administered every four weeks (Trial 4). Incidence 1% to 10% Cardiovascular: vasodilation, tachycardia, deep vein thrombosis, hypotension, cardiac arrest. Digestive: oral moniliasis, mouth ulceration, esophagitis, dysphagia, rectal bleeding, ileus.
Hematologic and Lymphatic: ecchymosis. Metabolic and Nutritional: dehydration, weight loss, hyperbilirubinemia, hypokalemia, hypercalcemia, hyponatremia. Nervous: somnolence, dizziness, depression.
Respiratory: rhinitis, pneumonia, sinusitis, epistaxis. Skin and Appendages: pruritus, skin discoloration, vesiculobullous rash, maculopapular rash, exfoliative dermatitis, herpes zoster, dry skin, herpes simplex, fungal dermatitis, furunculosis, acne. Special Senses: conjunctivitis, taste perversion, dry eyes.
Urinary: urinary tract infection, hematuria, vaginal moniliasis. Adverse reactions led to discontinuation of treatment in 5% of patients with AIDS-related Kaposi’s sarcoma and included myelosuppression, cardiac adverse reactions, infusion-related reactions, toxoplasmosis, HFS, pneumonia, cough/dyspnea, fatigue, optic neuritis, progression of a non-KS tumor, allergy to penicillin, and unspecified reasons. Table 5 and Table 6 summarize adverse reactions reported in patients treated with DOXIL liposomal infusion for AIDS-related Kaposi’s sarcoma in a pooled analysis of the four trials.
Table 5: Hematologic Adverse Reactions Reported in Patients With AIDS-Related Kaposi’s Sarcoma of Patients With AIDS-Related Kaposi’s Sarcoma The following additional adverse reactions were observed in 705 patients with AIDS-related Kaposi’s sarcoma. Incidence 1% to 5% Body as a Whole: headache, back pain, infection, allergic reaction, chills. Cardiovascular: chest pain, hypotension, tachycardia.
Cutaneous: herpes simplex, rash, itching. Digestive: mouth ulceration, anorexia, dysphagia. Metabolic and Nutritional: SGPT increase, weight loss, hyperbilirubinemia.
Other: dyspnea, pneumonia, dizziness, somnolence. Incidence Less Than 1% Body As A Whole: sepsis, moniliasis, cryptococcosis. Cardiovascular: thrombophlebitis, cardiomyopathy, palpitation, bundle branch block, congestive heart failure, heart arrest, thrombosis, ventricular arrhythmia.
Digestive: hepatitis. Metabolic and Nutritional Disorders: dehydration. Respiratory: cough increase, pharyngitis.
Skin and Appendages: maculopapular rash, herpes zoster. Special Senses: taste perversion, conjunctivitis. In this trial, patients in the DOXIL liposomal infusion + bortezomib combination group were treated for a median number of 4.5 months range Black, and 4% Asian and Other.
Table 7 lists adverse reactions reported in 10% or more of patients treated with DOXIL liposomal infusion in combination with bortezomib for multiple myeloma. Table 7: Frequency of Treatment-Emergent Adverse Reactions Reported in ≥10% Patients Treated for Multiple Myeloma With DOXIL Liposomal Infusion in Combination With Bortezomib 0
Postmarketing Experience
The following additional adverse reactions have been identified during postapproval use of DOXIL liposomal infusion. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Musculoskeletal and Connective Tissue Disorders: muscle spasms Respiratory, Thoracic and Mediastinal Disorders: pulmonary embolism (in some cases fatal) Hematologic Disorders: Secondary acute myelogenous leukemia Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens‑Johnson syndrome, toxic epidermal necrolysis, lichenoid keratosis Secondary Oral Neoplasms:.
| DOXIL Liposomal Infusion Patients (n=239) | Topotecan Patients (n=235) | |
|---|---|---|
| Neutropenia | ||
| 500 – <1000/mm 3 | 8% | 14% |
| <500/mm 3 | 4.2% | 62% |
| Anemia | ||
| 6.5 – <8 g/dL | 5% | 25% |
| < 6.5 g/dL | 0.4% | 4.3% |
| Thrombocytopenia | ||
| 10,000 – <50,000/mm 3 | 1.3% | 17% |
| <10,000/mm 3 | 0.0% | 17% |
| Non-Hematologic Adverse Reaction 10% or Greater | DOXIL Liposomal Infusion (%) treated (n=239) | Topotecan (%) treated (n=235) | ||
|---|---|---|---|---|
| All grades | Grades 3–4 | All grades | Grades 3–4 | |
| Body as a Whole | ||||
| Asthenia | 40 | 7 | 52 | 8 |
| Fever | 21 | 0.8 | 31 | 6 |
| Mucous Membrane Disorder | 14 | 3.8 | 3.4 | 0 |
| Back Pain | 12 | 1.7 | 10 | 0.9 |
| Infection | 12 | 2.1 | 6 | 0.9 |
| Headache | 11 | 0.8 | 15 | 0 |
| Digestive | ||||
| Nausea | 46 | 5 | 63 | 8 |
| Stomatitis | 41 | 8 | 15 | 0.4 |
| Vomiting | 33 | 8 | 44 | 10 |
| Diarrhea | 21 | 2.5 | 35 | 4.2 |
| Anorexia | 20 | 2.5 | 22 | 1.3 |
| Dyspepsia | 12 | 0.8 | 14 | 0 |
| Nervous | ||||
| Dizziness | 4.2 | 0 | 10 | 0 |
| Respiratory | ||||
| Pharyngitis | 16 | 0 | 18 | 0.4 |
| Dyspnea | 15 | 4.1 | 23 | 4.3 |
| Cough increased | 10 | 0 | 12 | 0 |
| Skin and Appendages | ||||
| Hand-foot syndrome | 51 | 24 | 0.9 | 0 |
| Rash | 29 | 4.2 | 12 | 0.4 |
| Alopecia | 19 | N/A | 52 | N/A |
| Patients With Refractory or Intolerant AIDS-Related Kaposi’s Sarcoma (n=74 This includes a subset of subjects who were 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. ) | Total Patients With AIDS-Related Kaposi’s Sarcoma (n=720 This includes only subjects with AIDS-KS who had available data from the 4 pooled trials. ) | |
|---|---|---|
| Neutropenia | ||
| < 1000/mm 3 | 46% | 49% |
| < 500/mm 3 | 11% | 13% |
| Anemia | ||
| < 10 g/dL | 58% | 55% |
| < 8 g/dL | 16% | 18% |
| Thrombocytopenia | ||
| < 150,000/mm 3 | 61% | 61% |
| < 25,000/mm 3 | 1.4% | 4.2% |
| Adverse Reactions | Patients With Refractory or Intolerant AIDS-Related Kaposi’s Sarcoma (n=77 This includes a subset of subjects who were 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. ) | Total Patients With AIDS-Related Kaposi’s Sarcoma (n=705 This includes only subjects with AIDS-KS who had available adverse event data from the 4 pooled trials. ) |
|---|---|---|
| Nausea | 18% | 17% |
| Asthenia | 7% | 10% |
| Fever | 8% | 9% |
| Alopecia | 9% | 9% |
| Alkaline Phosphatase Increase | 1.3% | 8% |
| Vomiting | 8% | 8% |
| Diarrhea | 5% | 8% |
| Stomatitis | 5% | 7% |
| Oral Moniliasis | 1.3% | 6% |
| Adverse Reaction | DOXIL Liposomal Infusion + bortezomib (n=318) | Bortezomib (n=318) | ||
|---|---|---|---|---|
| Any (%) | Grade 3–4 | Any (%) | Grade 3–4 | |
| Blood and lymphatic system disorders | ||||
| Neutropenia | 36 | 32 | 22 | 16 |
| Thrombocytopenia | 33 | 24 | 28 | 17 |
| Anemia | 25 | 9 | 21 | 9 |
| General disorders and administration site conditions | ||||
| Fatigue | 36 | 7 | 28 | 3 |
| Pyrexia | 31 | 1 | 22 | 1 |
| Asthenia | 22 | 6 | 18 | 4 |
| Gastrointestinal disorders | ||||
| Nausea | 48 | 3 | 40 | 1 |
| Diarrhea | 46 | 7 | 39 | 5 |
| Vomiting | 32 | 4 | 22 | 1 |
| Constipation | 31 | 1 | 31 | 1 |
| Mucositis/Stomatitis | 20 | 2 | 5 | <1 |
| Abdominal pain | 11 | 1 | 8 | 1 |
| Infections and infestations | ||||
| Herpes zoster | 11 | 2 | 9 | 2 |
| Herpes simplex | 10 | 0 | 6 | 1 |
| Investigations | ||||
| Weight decreased | 12 | 0 | 4 | 0 |
| Metabolism and Nutritional disorders | ||||
| Anorexia | 19 | 2 | 14 | <1 |
| Nervous system disorders | ||||
| Peripheral Neuropathy Peripheral neuropathy includes the following adverse reactions: peripheral sensory neuropathy, neuropathy peripheral, polyneuropathy, peripheral motor neuropathy, and neuropathy NOS. | 42 | 7 | 45 | 11 |
| Neuralgia | 17 | 3 | 20 | 4 |
| Paresthesia/dysesthesia | 13 | <1 | 10 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 18 | 0 | 12 | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash Rash includes the following adverse reactions: rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic, exfoliative rash, and rash generalized. | 22 | 1 | 18 | 1 |
| Hand-foot syndrome | 19 | 6 | <1 | 0 |
Warnings & Cautions for Doxil
Cardiomyopathy
Doxorubicin hydrochloride can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin hydrochloride is generally proportional to the cumulative exposure. Include prior use of other anthracyclines or anthracenediones in calculations of cumulative dose.
The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. In a clinical study in 250 patients with advanced cancer who were treated with DOXIL liposomal infusion, the risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between. Cardiomyopathy was defined as >20% decrease in resting left ventricular ejection fraction (LVEF) from baseline where LVEF remained in the normal range or a >10% decrease in LVEF from baseline where LVEF was less than the institutional lower limit of normal.
Two percent of patients developed signs and symptoms of congestive heart failure without documented evidence of cardiomyopathy. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL liposomal infusion, during treatment to detect acute changes, and after treatment to detect delayed cardiomyopathy.
Administer DOXIL liposomal infusion to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.
Infusion-Related Reactions
Serious, life-threatening, and fatal infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL liposomal infusion: 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. Of 239 patients with ovarian cancer treated with DOXIL liposomal infusion in Trial 4, 7% of patients experienced acute infusion-related reactions resulting in dose interruption. All occurred during cycle 1 and none during subsequent cycles.
Across multiple studies of DOXIL liposomal infusion monotherapy including this and other studies enrolling 760 patients with various solid tumors, 11% of patients had infusion-related reactions. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment are available for immediate use prior to initiation of DOXIL liposomal infusion.
Initiate DOXIL liposomal infusions at a rate of 1 mg/min and increase rate as tolerated. Withhold DOXIL liposomal infusion for Grade 1, 2, or 3 infusion-related reactions and resume at a reduced infusion rate. HFS or other skin toxicity required discontinuation of DOXIL liposomal infusion in 4.2% of patients.
HFS was generally observed after 2 or 3 cycles of treatment but may occur earlier. Delay DOXIL liposomal infusion for the first episode of Grade 2 or greater HFS. Discontinue DOXIL liposomal infusion if HFS is severe and debilitating.
Secondary Oral Neoplasms
Secondary oral cancers, primarily squamous cell carcinoma, have been reported from post-marketing experience in patients with long-term (more than one year) exposure to DOXIL liposomal infusion. These malignancies were diagnosed both during treatment with DOXIL liposomal infusion and up to 6 years after the last dose. Examine patients at regular intervals for the presence of oral ulceration or with any oral discomfort that may be indicative of secondary oral cancer.
The altered pharmacokinetics and preferential tissue distribution of liposomal doxorubicin that contributes to enhanced skin toxicity and mucositis compared to free doxorubicin may play a role in the development of oral secondary malignancies with long-term use.
Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, DOXIL liposomal infusion can cause fetal harm when administered to a pregnant woman; avoid the use of DOXIL liposomal infusion during the 1 st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2 nd and 3 rd trimesters. At doses approximately 0.12 times the recommended clinical dose, DOXIL liposomal infusion was embryotoxic and abortifacient in rabbits.
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 liposomal infusion.
Drug Interactions with Doxil
No formal drug interaction studies have been conducted with DOXIL liposomal infusion.
Pregnancy Safety for Doxil
Pregnancy Risk Summary Based on findings in animals and its mechanism of action, DOXIL liposomal infusion can cause fetal harm when administered to a pregnant woman; avoid the use of DOXIL liposomal infusion during the 1 st trimester. In animal reproduction studies, DOXIL liposomal infusion was embryotoxic in rats and abortifacient in rabbits following intravenous administration during organogenesis at doses approximately 0.12 times the recommended clinical dose (see Data ). Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2 nd and 3 rd trimesters.
Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2–4% and of miscarriage is 15–20% of clinically recognized pregnancies.
Embryotoxicity was characterized by increased embryo-fetal deaths and reduced live litter sizes.
Pediatric Use of Doxil
Pediatric Use The safety and effectiveness of DOXIL liposomal infusion in pediatric patients have not been established.
Contraindications for Doxil
- DOXIL liposomal infusion is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin hydrochloride.
- Hypersensitivity reactions to doxorubicin hydrochloride or the components of DOXIL liposomal infusion
Overdosage Information for Doxil
Acute overdosage with doxorubicin hydrochloride causes increased risk of severe mucositis, leukopenia, and thrombocytopenia.
Clinical Studies of Doxil
Multiple Myeloma
The efficacy of DOXIL liposomal infusion 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 who maintained a response were allowed to receive further treatment. The median number of cycles in each treatment arm was 5 (range 1–18).
The baseline demographics and clinical characteristics of the patients with multiple myeloma were similar between treatment arms ( Table 12 ). Table 12: Summary of Baseline Patient and 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.
The combination arm demonstrated significant improvement in TTP. As the prespecified primary objective was achieved at the interim analysis, patients in the bortezomib monotherapy group were then allowed to receive the DOXIL liposomal infusion + bortezomib combination. Efficacy results are as shown in Table 13 and Figure 1.
Table 13: Efficacy of DOXIL Liposomal Infusion in Combination With Bortezomib in the Treatment of Patients With Multiple Myeloma At the final analysis of survival, 78% of subjects in the DOXIL liposomal infusion 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 DOXIL liposomal infusion 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.
Seventy-eight percent of subjects in the DOXIL liposomal infusion and bortezomib combination therapy group and 80% of subjects in the bortezomib monotherapy group had received subsequent therapy. Figure 1
| Trial 1 (U.S.) N=27 | Trial 2 (U.S.) N=82 | Trial 3 (non-U.S.) N=36 | |
|---|---|---|---|
| Response Rate | 22.2% | 17.1% | 0% |
| 95% Confidence Interval | 8.6% – 42.3% | 9.7% – 27.0% | 0.0% – 9.7% |
| Protocol Defined ITT Population | ||
|---|---|---|
| DOXIL Liposomal Infusion (n=239) | Topotecan (n=235) | |
| TTP (Protocol Specified Primary Endpoint) | ||
| Median (Months) Kaplan-Meier estimates. | 4.1 | 4.2 |
| p-value p-value is based on the stratified log-rank test. | 0.62 | |
| Hazard Ratio Hazard ratio is based on Cox proportional-hazard model with the treatment as single independent variable. A hazard ratio less than 1 indicates an advantage for DOXIL liposomal infusion. | 0.96 | |
| 95% CI for Hazard Ratio | (0.76, 1.20) | |
| Overall Survival | ||
| Median (Months) | 14.4 | 13.7 |
| p-value p-value not adjusted for multiple comparisons. | 0.05 | |
| Hazard Ratio | 0.82 | |
| 95% CI for Hazard Ratio | (0.68, 1.00) | |
| Response Rate | ||
| Overall Response n (%) | 47 (19.7) | 40 (17.0) |
| Complete Response n (%) | 9 (3.8) | 11 (4.7) |
| Partial Response n (%) | 38 (15.9) | 29 (12.3) |
| Median Duration of Response (Months) | 6.9 | 5.9 |
| Investigator Assessment | All Evaluable Patients (n=34) | Evaluable Patients Who Received Prior Doxorubicin (n=20) |
| Response There were no complete responses in this population. | ||
| Partial (PR) | 27% | 30% |
| Stable | 29% | 40% |
| Progression | 44% | 30% |
| Duration of PR (Days) | ||
| Median | 73 | 89 |
| Range | 42+ – 210+ | 42+ – 210+ |
| Time to PR (Days) | ||
| Median | 43 | 53 |
| Range | 15 – 133 | 15 – 109 |
| Indicator Lesion Assessment | All Evaluable Patients (n=42) | Evaluable Patients Who Received Prior Doxorubicin (n=23) |
| Response | ||
| Partial (PR) | 48% | 52% |
| Stable | 26% | 30% |
| Progression | 26% | 17% |
| Duration of PR (Days) | ||
| Median | 71 | 79 |
| Range | 22+ – 210+ | 35 – 210+ |
| Time to PR (Days) | ||
| Median | 22 | 48 |
| Range | 15 – 109 | 15 – 109 |
| Patient Characteristics | DOXIL Liposomal Infusion + bortezomib n=324 | bortezomib n=322 |
|---|---|---|
| Median age in years (range) | 61 (28, 85) | 62 (34, 88) |
| % Male/female | 58 / 42 | 54 / 46 |
| % Caucasian/Black/other | 90 / 6 / 4 | 94 / 4 / 2 |
| Disease Characteristics | ||
| % with IgG/IgA/Light chain | 57 / 27 / 12 | 62 / 24 / 11 |
| % β 2 -microglobulin group | ||
| ≤2.5 mg/L | 14 | 14 |
| >2.5 mg/L and ≤5.5 mg/L | 56 | 55 |
| >5.5 mg/L | 30 | 31 |
| Serum M-protein (g/dL): Median (Range) | 2.5 (0–10.0) | 2.7 (0–10.0) |
| Urine M-protein (mg/24 hours): Median (Range) | 107 (0–24883) | 66 (0–39657) |
| Median Months Since Diagnosis | 35.2 | 37.5 |
| % Prior Therapy | ||
| One | 34 | 34 |
| More than one | 66 | 66 |
| Prior Systemic Therapies for Multiple Myeloma | ||
| Corticosteroid (%) | 99 | >99 |
| Anthracyclines | 68 | 67 |
| Alkylating agent (%) | 92 | 90 |
| Thalidomide/lenalidomide (%) | 40 | 43 |
| Stem cell transplantation (%) | 57 | 54 |
| Endpoint | DOXIL Liposomal Infusion + bortezomib n=324 | Bortezomib n=322 |
|---|---|---|
| Time to Progression Kaplan Meier estimate. | ||
| Progression or death due to progression (n) | 99 | 150 |
| Censored (n) | 225 | 172 |
| Median in days (months) | 282 (9.3) | 197 (6.5) |
| 95% CI | 250; 338 | 170; 217 |
| Hazard ratio Hazard ratio based on stratified Cox proportional hazards regression. A hazard ratio < 1 indicates an advantage for DOXIL liposomal infusion +bortezomib. | 0.55 | |
| (95% CI) | (0.43, 0.71) | |
| p-value Stratified log-rank test. | <0.001 | |
| Response (n) RR as per EBMT criteria. | 303 | 310 |
| % Complete Response (CR) | 5 | 3 |
| % Partial Response (PR) | 43 | 40 |
| % CR + PR | 48 | 43 |
| p-value Cochran-Mantel-Haenszel test adjusted for the stratification factors. | 0.25 | |
| Median Duration of Response (months) | 10.2 | 7.0 |
| (95% CI) | (10.2; 12.9) | (5.9; 8.3) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Doxil?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Doxil Prices