Doxorubicin (Adriamycin)

General information

Class/mechanism: Anthracycline; binds and intercalates into DNA, inhibiting nucleotide replication and DNA/RNA polymerase activity. Intercalation of DNA triggers DNA cleavage via topoisomerase II. Toxic effects on organs may be related to cell membrane lipid binding activities; enzymatic electron reduction of doxorubicin creates reactive species, e.g. hydroxyl free radicals OH-, which has been implicated in cardiotoxicity by means of Cu (II) and Fe (III) reduction.
Route: IV
Extravasation: vesicant

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Hepatocellular carcinoma
• Non-Hodgkin lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Peripheral T-cell lymphoma
• Osteosarcoma

Diseases for which it is used

• Adrenocortical carcinoma
• Adult T-cell leukemia-lymphoma
• Anaplastic large cell lymphoma
• B-cell acute lymphoblastic leukemia
• Bladder cancer
• Breast cancer
• Burkitt lymphoma
• Cutaneous basal cell carcinoma
• Cutaneous squamous cell carcinoma
• Diffuse large B-cell lymphoma
• Endometrial cancer
• Ewing sarcoma
• Hepatoblastoma
• HIV-associated lymphoma
• Classical Hodgkin lymphoma
• Hodgkin lymphoma, nodular lymphocyte-predominant
• Kaposi sarcoma
• Malignant pleural mesothelioma
• Marginal zone lymphoma
• Mediastinal gray-zone lymphoma
• Multiple myeloma
• Neuroblastoma
• Pancreatic NET
• Post-transplant lymphoproliferative disorder
• Primary mediastinal B-cell lymphoma
• Rhabdomyosarcoma
• Sarcomatoid renal cell carcinoma
• Soft tissue sarcoma
• Thymoma
• Transformed lymphoma
• Transplant conditioning regimens
• Waldenström macroglobulinemia

Diseases for which it was used

• Acute myeloid leukemia
• Chronic lymphocytic leukemia
• Gastric cancer
• Non-small cell lung cancer
• Ovarian cancer
• Prostate cancer
• Small cell lung cancer
• Testicular cancer

Patient drug information

• Doxorubicin (Adriamycin) patient drug information (Chemocare)
• Doxorubicin (Adriamycin) package insert page 1
• Doxorubicin (Adriamycin) patient drug information (UpToDate)

History of changes in FDA indication

• 1974-08-07: Initial FDA approval
• 2003-05-08: Earliest date with label information at Drugs @ FDA: "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. (No supporting studies are cited)
• Uncertain date: 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. (Based on EBCTCG meta-analysis)

History of changes in EMA indication

• 1996-06-21: EURD

History of changes in PMDA indication

• 2014-12-18: Revised indication and a new dosage for the relief of symptoms of malignant lymphoma.

Also known as

• Code name: FI-106
• Generic names: ADM, doxorubicin hydrochloride, hydroxydaunorubicin
• Brand names:

Synonyms
Adriablastina	Adriacept	Adriacin	Adriamycin	Adriamycine	Adriblastin	Adriblastina	Adriblastine
Adricept	Adricin	Adrim	Adrimedac	Adrosal	Antraciclin	Biorrub	Biorubina
Cadria	Carcinocin	Cloridrato DE	Doxorrubicina Colhidrol	Deldoxin	Dicladox	Dobicin	Dobixin
Doxo	Doxobin	Doxo Cell	Doxocris	Doxokebir	Doxolem	Doxonolver	Doxor
Doxorrubicina	Doxoruben	Doxorubicina	Doxorubicine	Doxorubicinum	Doxorubin	Doxotec	Doxtie
Duxocin	Evacet	Farmiblastina	Fauldoxo	Flavicina	Ifadox	Kemodoxa	Lyphidox
Nagun	Neoxane	Nuaze	Oncodria	Onkodox	Onkostatil	Pallagicin	Ranxas
Rastocin	Ribodoxo	Roxorin	Rubex	Varidoxo	Zodox

References

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. link to original article PubMed

Note: it is not entirely clear which EBCTCG meta-analysis was used to support the FDA indication; there have been multiple EBCTCG meta-analyses over the years and this one is representative.