EtoposideEdit

Etoposide is a semi-synthetic chemotherapeutic agent used in the treatment of several cancers. It is a derivative of the natural product podophyllotoxin and acts as a topoisomerase II inhibitor, interrupting the normal unwinding and resealing of DNA during replication. By promoting DNA breaks in rapidly dividing cells, etoposide helps to slow or halt tumor growth when used as part of combination chemotherapy. The drug is available in multiple formulations for different routes of administration, including intravenous and oral forms, and has a long-standing role in oncologic regimens around the world. Etoposide is typically used as part of broader treatment plans rather than as a stand-alone cure, reflecting the reality that cancer therapy commonly relies on multi-drug strategies to maximize tumor kill while managing toxicity. podophyllotoxin mayapple topoisomerase II DNA

The principal mechanism of action for etoposide centers on its interaction with the cellular enzyme topoisomerase II. In normal cells, topoisomerase II relieves torsional strain in DNA during replication by creating transient double-strand breaks, passing another DNA helix through the break, and then resealing the cut. Etoposide interferes with this process by stabilizing the transient enzyme-DNA complex, effectively converting a reversible nick into a persistent double-strand break. This results in replication arrest and cell death in rapidly proliferating cancer cells. Because these effects are more pronounced in cells undergoing division, etoposide is particularly useful against tumors with high mitotic rates. topoisomerase II DNA

Medical uses

  • Indications and common regimens: Etoposide is a key component in several established chemotherapy regimens. It is used in germ cell tumors such as testicular cancer, most notably in the BEP regimen (bleomycin, etoposide, cisplatin). It is also employed in small cell lung cancer regimens, typically in combination with cisplatin or carboplatin. Additionally, etoposide features in regimens for some aggressive non-Hodgkin lymphomas, as well as other malignancies where multi-agent chemotherapy is the standard approach. testicular cancer BEP regimen small cell lung cancer non-Hodgkin lymphoma CHOP chemotherapy EPOCH chemotherapy

  • Formulations and administration: Etoposide is marketed in several forms, including an intravenous preparation (Toposar) and an oral capsule (VePesid). A water-soluble prodrug form (etoposide phosphate, sold under names such as Etopophos) enables alternative administration routes and can influence pharmacokinetics. Dosing is guided by body surface area, organ function, prior therapies, and the specific cancer being treated. Toposar VePesid etoposide phosphate pharmacokinetics

Safety and adverse effects

  • Hematologic toxicity: The most significant toxicity is myelosuppression, which can manifest as neutropenia, anemia, or thrombocytopenia. This bone marrow suppression underpins infection risk and the need for careful monitoring during cycles of therapy. myelosuppression

  • Other adverse effects: Patients may experience nausea, vomiting, mucositis, fatigue, fever, and hair loss. There is also a risk of hypersensitivity reactions with certain IV preparations, as well as local tissue injury if the drug leaks from the vein (extravasation). Long-term use or high cumulative exposure carries a risk of therapy-related secondary malignancies, including therapy-related leukemia or myelodysplastic syndromes. Reproductive and fetal safety is a concern, and the drug is generally avoided in pregnancy unless clearly indicated with a risk-benefit assessment. nausea vomiting mucositis myelosuppression secondary malignancy leukemia teratogenicity

Pharmacokinetics and pharmacodynamics

  • Absorption and distribution: Oral etoposide is absorbed variably, with bioavailability influenced by factors such as food and gastric pH. Intravenous administration provides immediate systemic exposure. The drug distributes widely through body tissues and crosses into various organs. bioavailability pharmacokinetics

  • Metabolism and excretion: Etoposide is largely metabolized in the liver and eliminated via renal and biliary routes. Dose adjustments may be needed for hepatic or kidney impairment. Drug interactions with other agents that share metabolic pathways can alter etoposide levels and toxicity. hepatic metabolism renal excretion drug interactions

  • Resistance: Tumor cells can develop resistance through multiple mechanisms, including reduced drug uptake, increased drug efflux, altered topoisomerase II activity, and enhanced DNA repair. These factors influence how well etoposide works in a given patient and help explain why combination regimens remain standard practice. drug resistance

History and regulatory status

  • Development and approvals: Etoposide emerged in the late 20th century as a clinically useful topoisomerase II inhibitor and has since become a staple in oncologic regimens worldwide. It has been approved for various indications and remains a component of many established protocols. The drug’s use has evolved with improvements in supportive care, dosing strategies, and combination regimens. podophyllotoxin FDA approval

  • Prophylaxis and safety considerations: Ongoing clinical experience emphasizes balancing efficacy with toxicity management, including monitoring blood counts, supporting patients with growth factors or transfusions when appropriate, and adherent to guidelines for administration to minimize risks such as extravasation and secondary cancers. bone marrow suppression extravasation

See also