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Generic Name: Doxorubicin
Brand Name(s): Adriamycin®, Rubex®, Doxil®
IUPAC: (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
FDA Approval: yes
Manufacturer Link
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Usage: Doxorubicin is useful in a wide range of cancers and only a few cancer types are unresponsive to the drug. These unresponsive types include colon cancer, melanoma, chronic leukemias and renal cancer. Cancers for which doxorubicin is used include: Hodgkin's and non-Hodgkin's
lymphoma, breast cancer, ovarian cancer, testicular cancer, acute
leukemia, soft tissue
sarcoma, lung cancer, bladder cancer, gastric (stomach) cancer, thyroid cancer, hepatoma, Wilm's tumor and neuroblastoma. In 2007 the FDA also approved doxorubicine in combination with bortezomib for the treatment of
multiple myeloma.
(1) Doxorubicin is administered intravenously. In a newer formulation, Doxil, the drug is surrounded by a
lipid 'bubble' (membrane). This formulation is an attempt to reduce the toxicity of the drug by blocking its effects on normal tissues.
Mechanism: Doxorubicin is an anthracycline antibiotic that exerts its effects on cancer cells via two different mechanisms. It acts as an intercalating agent and wedges between the
DNA bases thus blocking DNA synthesis and
transcription. The drug also inhibits the activity of an
enzyme,
topoisomerase type II. This leads to breaks in the genomic DNA. Both of these mechanisms result in DNA disruption that ultimately can lead to the death of the cell. Interestingly, several studies have reported that green tea enhances the antitumor activity of doxorubicin.
(2)(3) Epirubicin (Ellence®) is another anthracycline derivative with similar biological activity. It also intercalates into DNA and interferes with cellular processes.
(4)
Side Effects: Common side effects include: "
Radiation recall" (can bring back skin damage from previous radiation therapy), decreased blood cell counts, increased risk of infection and bleeding, loss of appetite, stomatitis, alopecia (hair loss), Nausea and vomiting, mouth sores, Birth defects, liver toxicity, and acute arrhythmia. Cardiac toxicity becomes relevant at high doses. If present, the cardiomyopathy may lead to irreversible congestive heart failure.
(5) Due to this concern, patients should talk to their doctors about any cardiac conditions or complications. Slow intravenous infusion can reduce cardiac toxicity (by lowering blood concentrations of the drug). However, this method can be problematic because it lasts for 48-96 hours.
(6) Birth defects are a possibility for the children of women that receive doxrubicin while pregnant. Patients should not plan to become pregnant or father a child during use. There may be more severe complication if a patient has other health problems, such as, chickenpox, heart disease or heart failure, gout, shingles, kidney stones or liver disease. For this reason patients should discuss these health risks with their physician before beginning treatment.
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