In some studies, patient toxicity reviews were obtained by a diary with the important information before and after each cycle of chemotherapy and their consequences.Common toxicities are neutropenia (<1 × 109 cells/L) without any death related and in lesser mesures anemia and thrombocytopenia.The most acute dose-limiting toxicity of epirubicin is bone marrow suppression, irreversible cardiotoxicity such as an important chronic cumulative dose-limiting toxicity illness and myelosuppression. The last one is associated with leukopenia, the decrease in the number of leukocytes (white blood cells) in the blood. Chemistry
Epirubicin is a 4-epi-isomer of doxorubicin and a derivative of daunorubicin. As an anthracycline antibiotic it belongs to several chemical classes such as: aminoglycosides, tetracene quinones, p-quinones, primary alpha-hydroxy ketone and tertiary alpha-hydroxy ketones. Due to numerous ionisable groups, it has multiple pka (pKa1 = 9.17 (phenol); pKa2 = 9.93 (amine); pKa3 = 12.67 (hydroxyl)) and is soluble in a variety of solvents (DMSO 125 mg/mL; Ethanol 120 mg/mL; In water, 93 mg/L at 25 °C (est)). It has a melting point of 344.53 and a boiling point of 810.3±65.0 °C at 760 mmHg.Its shelf life (def. as the time it takes to degrade 10% from the initial concentration) has been documented as at least 14 and 180 days at 25 °C and 4 °C, respectively in a 0.9% sodium chloride solution in polypropylene syringes. Synthesis
There are multiple ways of synthesizing epirubicin depending on which starting material is used as a precursor.
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.