- 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.
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.
Published Studies Related to Doxorubicin
First-line treatment of metastatic or locally advanced unresectable soft tissue
sarcomas with conatumumab in combination with doxorubicin or doxorubicin alone: a
phase I/II open-label and double-blind study. 
sarcoma... INTERPRETATION: Addition of conatumumab to doxorubicin appeared to be safe but
A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma. [2011.12]
Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL-DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated... Cardiotoxicity was not seen in either treatment groups.
Hepatic arterial infusion of doxorubicin-loaded microsphere for treatment of hepatocellular cancer: a multi-institutional registry. [2011.10]
BACKGROUND: Hepatic intra-arterial therapy for unresectable hepatocellular cancer (HCC) has been shown to improve overall survival, but can have significant toxicity. A recent prospective randomized controlled trial demonstrated superior response rates and significantly less morbidity and doxorubicin-related adverse events with drug-eluting beads with doxorubicin (DEBDOX) compared with conventional chemoembolization. The aim of this study was to confirm the efficacy of DEBDOX for the treatment of unresectable HCC... CONCLUSIONS: Hepatic intra-arterial injection of DEBDOX is safe and effective in the treatment of HCC, as demonstrated by a minimal complication rate and robust and durable tumor response. Copyright (c) 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression. [2011.08.15]
BACKGROUND: A rapid and early monoclonal (M) protein response during initial therapy in patients with multiple myeloma had been identified as a predictor of superior long-term outcome in some--but not all--studies... CONCLUSIONS: These analyses supported the possibility that a robust early M protein response is a good prognostic factor for long-term outcome of myeloma patients with relapsed and/or refractory disease receiving bortezomib or PLD + bortezomib. Copyright (c) 2011 American Cancer Society.
Lyso-thermosensitive liposomal doxorubicin: an adjuvant to increase the cure rate of radiofrequency ablation in liver cancer. [2011.08]
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide...
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
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
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
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 TelcytaŽ + 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 TelcytaŽ 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.
Page last updated: 2013-02-10