It was first observed in adult cancer patients as clinical congestive heart failure (CHF), characterized by pulmonary oedema, fluid overload, and effort intolerance, was initially reported in 1979 by Von Hoff et al. at 2.2% overall with a cumulative doxorubicin dose-dependent incidence of CHF of 3%, 7%, and 18% at 400, 550, and 700 mg/m2, respectively.There are a lot of adverse effects of epirubicin related with the dose-limiting. The major commun negative effects are fever, diarrhea, nausea and vomiting. More than 50% of patients without a right prophylactic antiemetics therapy experience nausea and vomiting the first 24 h after administration. That fact occurs if the epirubicin dose is between 50 to 75 mg/m2 single doses.Reversible alopecia and local cutaneous reactions are important adverse effects too. Those could be related with radiation recall and local reactions such as cellulitis, which cause development of tissue necrosis and pain if extravasation damage occurs.Another major adverse effects are cumulative dose-related cardiotoxicity and acute dose-limiting haematotoxicity. This last is related to mucositis, inflammation and ulceration in mouth or mucous membranes.Finally, the most adverse effect is secondary leukemia produced by breast cancer treated with epirubicin, particularly in those cases in which the patient receives concomitant alkylating agent therapy. Toxicity
Epirubicins toxicity is according to the NCI-CTEP Common Toxicity Criteria, version 2.0.
The reduction to alcohol is performed with a derivative of a borohydride of an alkali metal with formula MHBL3, where M=Li, Na, K; L=AlkO, AlkCOO, ArCOO. The subsequent halogenation is performed with a complex halogenating agent where an H or a chain of up to 4 carbons is combined with Cl, I or Br. The final hydrolysis is analogous to the one in the first pathway. Development history
The first trial of epirubicin in humans was published in 1980. Upjohn applied for approval by the U.S. Food and Drug Administration (FDA) in node-positive breast cancer in 1984, but was turned down because of lack of data. In 1999 Pharmacia (who had by then merged with Upjohn) received FDA approval for the use of epirubicin as a component of adjuvant therapy in node-positive patients. Patent protection for epirubicin expired in August 2007. == References ==