WARNING
- Severe local tissue necrosis will occur if there is extravasation during administration (see DOSAGE AND ADMINISTRATION). Doxorubicin must not be given by the intramuscular or subcutaneous route.
- Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure (CHF) may occur either during therapy or months to years after termination of therapy. The probability of developing impaired myocardial function based on a combined index of signs, symptoms and decline in left ventricular ejection fraction (LVEF) is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin, 3 to 5% at a dose of 400 mg/m2, 5 to 8% at 450 mg/m2 and 6 to 20% at 500 mg/m2. The risk of developing CHF increases rapidly with increasing total cumulative doses of doxorubicin in excess of 400 mg/m2. Risk factors (active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other cardiotoxic drugs) may increase the risk of cardiac toxicity. Cardiac toxicity with doxorubicin may occur at lower cumulative doses whether or not cardiac risk factors are present. Pediatric patients are at increased risk for developing delayed cardiotoxicity.
- Secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) has been reported in patients treated with anthracyclines, including doxorubicin (see ADVERSE REACTIONS). The occurrence of refractory secondary AML or MDS is more common when anthracyclines are given in combination with DNA-damaging anti-neoplastic agents or radiotherapy, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated. The rate of developing secondary AML or MDS has been estimated in an analysis of 8563 patients with early breast cancer treated in 6 studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), including NSABP B-15. Patients in these studies received standard doses of doxorubicin and standard or escalated doses of cyclophosphamide (AC) adjuvant chemotherapy and were followed for 61,810 patient years. Among 4483 such patients who received conventional doses of AC, 11 cases of AML or MDS were identified, for an incidence of 0.32 cases per 1000 patient years (95% CI 0.16–0.57) and a cumulative incidence at 5 years of 0.21% (95% CI 0.11–.41%). In another analysis of 1474 patients with breast cancer who received adjuvant treatment with doxorubicin-containing regimens in clinical trials conducted at University of Texas M.D. Anderson Cancer Center, the incidence was estimated at 1.5% at 10 years. In both experiences, patients who received regimens with higher cyclophosphamide dosages, who received radiotherapy, or who were aged 50 or older had an increased risk of secondary AML or MDS. Pediatric patients are also at risk of developing secondary AML.
- Dosage should be reduced in patients with impaired hepatic function.
- Severe myelosuppression may occur.
- Doxorubicin should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
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DOXORUBICIN SUMMARY
Doxorubicin Hydrochloride for Injection, USP
Doxorubicin Hydrochloride Injection, USP
Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Doxorubicin consists of a naphthacenequinone nucleus linked through a glycosidic bond at ring atom 7 to an amino sugar, daunosamine.
Doxorubicin has been used successfully to produce regression in disseminated neoplastic conditions such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types.
Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.
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NEWS HIGHLIGHTSMedia Articles Related to Doxorubicin
CytRx To Initiate Phase 2 Clinical Trial With INNO-206 In Patients With Advanced Gastric Cancer
Source: Health News from Medical News Today [2009.11.19]
CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical company, today announced plans to initiate an open-label, multinational Phase 2 clinical trial with its doxorubicin prodrug INNO-206 as a second-line treatment in patients with advanced gastric (stomach) cancer. CytRx President and CEO Steven A.
Published Studies Related to 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 Doxorubicin
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).
Vincristine, DOXIL® (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).
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.
A Comparison of DOX-SL Versus Adriamycin Plus Bleomycin Plus Vincristine in the Treatment of Severe AIDS-Related Kaposi's Sarcoma [Active, not recruiting]
To determine the efficacy of Stealth liposomal doxorubicin hydrochloride (DOX-SL) in the
treatment of severe AIDS-related Kaposi's sarcoma (KS) by comparison with the established
therapy ABV: Adriamycin (doxorubicin)/bleomycin/vincristine. To evaluate the safety and
tolerance of DOX-SL compared to ABV in a population of AIDS patients with severe KS.
Ph 3 Randomized Study of Telcyta® + Liposomal Doxorubicin Vs Liposomal Doxorubicin in Platinum Refractory or Resistant Ovarian Cancer [Active, not recruiting]
The purpose of this research study is to determine if Telcyta® given in combination with
liposomal doxorubicin is more effective than liposomal doxorubicin alone in treating women
who have recurrent ovarian epithelial cancer, fallopian tube cancer or primary peritoneal
cancer that is refractory or resistant to platinum chemotherapy.
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Page last updated: 2009-11-19
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