Anthracycline

Anthracyclines are a class of anticancer drugs used in chemotherapy. The core members include doxorubicin, daunorubicin, epirubicin, and idarubicin; other related agents such as mitoxantrone are sometimes grouped with this class. They are among the most effective treatments for a range of hematologic malignancies and solid tumors and are commonly used in combination regimens. Their therapeutic usefulness is tempered by dose-dependent toxicities, especially to the heart and bone marrow.

Mechanism and pharmacology: Anthracyclines act by intercalating into DNA, inhibiting topoisomerase II, and generating reactive oxygen species, which cause DNA damage and cell death. They are considered cell cycle-non-specific but are most impactful against rapidly dividing cells. They are usually given intravenously due to limited oral bioavailability. A hallmark concern is cumulative, dose-related cardiotoxicity, which can lead to dilated cardiomyopathy and heart failure, necessitating careful lifetime dosing and monitoring.

Clinical use and safety: Anthracyclines are used across many cancer types, including breast cancer, leukemias, lymphomas, sarcomas, and some solid tumors. Common adverse effects include myelosuppression, mucositis, nausea, vomiting, alopecia, and increased infection risk. A characteristic feature is red or orange discoloration of urine. Cardiotoxicity is a major dose-limiting toxicity; younger patients and those with prior chest irradiation or existing cardiac disease are at higher risk. Cardio-protective strategies include dose limitation, echocardiographic monitoring, and the use of dexrazoxane or liposomal formulations in select regimens. Extravasation of an anthracycline can cause tissue necrosis and requires prompt management.

Resistance and administration: Resistance can arise from reduced drug accumulation or alterations in topoisomerase II and drug efflux mechanisms. Anthracyclines are typically administered IV, with various formulations (including liposomal forms) designed to modify toxicity profiles. They are integral components of many regimens, such as those used in breast cancer, lymphomas, and leukemias.