WARNING: INFUSION REACTIONS, MYELOSUPPRESSION, CARDIOTOXICITY, LIVER IMPAIRMENT, ACCIDENTAL SUBSTITUTION
- The use of DOXIL (doxorubicin HCl liposome injection) may lead to cardiac toxicity. Myocardial damage may lead to congestive heart failure and may occur as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study in patients with advanced breast cancer, 250 patients received DOXIL at a starting dose of 50 mg/m2 every 4 weeks. At all cumulative anthracycline doses between 450–500 mg/m2 or between 500–550 mg/m2, the risk of cardiac toxicity for patients treated with DOXIL was 11%. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. Cardiac toxicity may also occur at lower cumulative doses in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy [ see Warnings and Precautions ].
- Acute infusion-related reactions including, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patients treated with DOXIL. In most patients, these reactions resolve over the course of several hours to a day once the infusion is terminated. In some patients, the reaction has resolved with slowing of the infusion rate. Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have been reported. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. DOXILshould be administered at an initial rate of 1 mg/min to minimize the risk of infusion reactions [ see Warnings and Precautions ].
- Severe myelosuppression may occur [ see Warnings and Precautions ].
- Dosage should be reduced in patients with impaired hepatic function [ see Dosage and Administration and Use in Specific Populations ].
- Accidental substitution of DOXIL for doxorubicin HCl has resulted in severe side effects. DOXIL should not be substituted for doxorubicin HCl on a mg per mg basis [ see Dosage and Administration ].
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DOXIL SUMMARY
WARNING: INFUSION REACTIONS, MYELOSUPPRESSION, CARDIOTOXICITY, LIVER IMPAIRMENT, ACCIDENTAL SUBSTITUTION
Doxil® (doxorubicin HCl liposome injection) is doxorubicin hydrochloride (HCl) encapsulated in STEALTH® liposomes for intravenous administration.
Doxil® (doxorubicin HCl liposome injection) is indicated for:
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The treatment of metastatic carcinoma of the ovary in patients with disease that is refractory to both paclitaxel- and platinum-based chemotherapy regimens. Refractory disease is defined as disease that has progressed while on treatment, or within 6 months of completing treatment.
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The treatment of AIDS-related Kaposi's sarcoma in patients with disease that has progressed on prior combination chemotherapy or in patients who are intolerant to such therapy.
These indications are based on objective tumor response rates. No results are available from controlled trials that demonstrate a clinical benefit resulting from this treatment, such as improvement in disease-related symptoms or increased survival.
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NEWS HIGHLIGHTSMedia Articles Related to Doxil (Doxorubicin)
Celsion Plans To Launch Phase II Program To Study ThermoDox(R) In Combination With RFA For Colorectal Liver Metastases
Source: Colorectal Cancer News From Medical News Today [2010.03.02]
Celsion Corporation (Nasdaq: CLSN) announced that it will initiate a Randomized Phase II Study of Lyso-Thermosensitive Liposomal Doxorubicin (ThermoDox®) and Radiofrequency Ablation (RFA) for Colorectal Liver Metastases (CRLM). Dr. Steven K...
Published Studies Related to Doxil (Doxorubicin)
Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. [2009.09]
RATIONALE: Canfosfamide HCl (CAN) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. CAN is synergistic in vitro with carboplatin, paclitaxel and anthracyclines... CONCLUSION: CAN was well tolerated. This is the first randomised study showing an increased OS with third-line therapy. This might have important consequences for other recurrent OC trials.
A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinoma. [2009.09]
Hepatocellular carcinoma (HCC) is a major and often therapeutically frustrating oncological problem. A total of 100 patients with unresectable HCC were recruited and randomized to be treated with either transcatheter arterial chemoembolization (TACE) or systemic chemotherapy... In this setting, serum albumin level is a candidate marker for selection of cases who may benefit from this procedure.
Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802). [2009.07]
BACKGROUND: This randomized, multicenter, phase III trial compared doxorubicin plus cyclophosphamide (AC), single-agent docetaxel (D), and an alternating regimen of AC and docetaxel (AC-D) as first-line chemotherapy in metastatic breast cancer (MBC)... CONCLUSION: There was no difference in the TTF among the three arms. However, there was a trend toward a better response and better OS in the D than in the AC.
Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: rationale and design of the LITE (Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot study. [2009.06.12]
BACKGROUND: Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Early detection at subclinical stage is pivotal to minimize the risk of overt cardiotoxicity. Liposomal anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity. OBJECTIVE: We designed a single-center randomized clinical trial, the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation (LITE) pilot study to compare the safety of liposomal doxorubicin vs standard epirubicin in terms of clinical and subclinical cardiotoxicity... CONCLUSIONS: Results of the LITE pilot study should provide important clinical and mechanistic insights on the promising role of liposomal anthracyclines in patients with breast cancer and indication to anthracycline chemotherapy (ClinicalTrials.gov identifier NCT00531973).
Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. [2009.05.20]
PURPOSE: To evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy... CONCLUSION: Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.
Clinical Trials Related to Doxil (Doxorubicin)
A Study Comparing the Combination of Doxil and Yondelis, to Doxil Alone for Subjects With Ovarian Cancer [Active, not recruiting]
The purpose of this research study is to determine if the combination of Yondelis and Doxil
is better at improving overall survival over Doxil alone in subjects with relapsed advanced
ovarian cancer.
Vincristine, DOXILŽ (Doxorubicin HCl Liposome Injection) and Dexamethasone vs. Vincristine, Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma [Completed]
The purpose of this study is to determine how well newly diagnosed multiple myeloma patients
respond to an experimental regimen of Vincristine, DOXIL (doxorubicin HCl liposome injection)
and Dexamethasone (VDD) versus the standard treatment of Vincristine, Doxorubicin and
Dexamethasone (VAD).
Randomized Phase II Trial of Doxil With or Without Dexamethasone for Metastatic Hormone Refractory Prostate Cancer [Terminated]
The primary objective of this study is to assess disease response to Doxil in patients with
hormone refractory prostate cancer with or without dexamethasone pre-treatment.
Study Design:
We will perform an open labeled, parallel, randomized phase II study using a two-stage design
to determine if there is sufficient anti-tumor activity in either arm to warrant further
study. Assumptions made in this study: an unacceptable overall response rate is /= 30%. Fifteen patients will be
randomized in the first phase (to both Arm 1 and Arm 2). No further patients will be accrued
if <2/15 responses are noted in a given arm. Ten additional patients will be enrolled if >/=
2/15 responses are observed. If there are >/= 5/25 responses then further studies will be
pursued with that regimen. We will determine the overall incidence & severity of toxicities
in both arms.
Treatment:
Arm 1: Doxil: Dose: 50 mg/m2, IV (in the vein) on day 5 of each 28 day cycle. Arm 2: Doxil:
Dose: 50 mg/m2, IV (in the vein) on day 5 of each 28 day cycle. Arm 1 only: Dexamethasone:
Dose: 12 mg twice a day by mouth on days 1, 2, 3, 4, 5 of each 28 day cycle.
Number of Cycles for both Arm 1 & 2: until progression or unacceptable toxicity develops.
Phase III Comparison of Adjuvant Chemotherapy W/High-Dose Cyclophosphamide Plus Doxorubicin (AC) vs Sequential Doxorubicin Fol by Cyclophosphamide (A-C) in High Risk Breast Cancer Patients With 0-3 Positive Nodes (Intergroup, CALGB 9394) [Active, not recruiting]
To compare disease-free survival (DFS), overall survival (s), and toxicity of high-isk
primary breast cancer patients with negative axillary lymph nodes or with one to three
positive nodes treated with adjuvant high-dose chemotherapy with doxorubicin plus
cyclophosphamide (AC), versus high-dose sequential chemotherapy with doxorubicin followed by
cyclophosphamide (A-->C).
Thalidomide + Dexamethasone vs. DOXIL (Doxorubicin HCl Liposome Injection) + Thalidomide + Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma [Active, not recruiting]
The main purpose of this study is to determine if Thalidomide + Dexamethasone or DOXIL
(doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone is more effective in
treating patients newly diagnosed with multiple myeloma. The number of patients whose
multiple myeloma disappears for a period of time (also called "Complete Response") will be
studied to make the determination of which treatment is more effective.
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Page last updated: 2010-03-02
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