Etoposide (VP-16). Etoposide is a natural product that derives from podophyllotoxin (see Fig. 2.11). Its mechanism of action is to cause single-strand and double-strand breaks in DNA through interaction with DNA topoisomerase II, inducing arrest in the G2-phase of the cell cycle [8,21,154]. This activity is mediated through the formation of a stable complex with DNA and topoisomerase II. In addition, etopo-side binds to tubulin and inhibits microtubular assembly. Although etoposide is highly lipophilic, it does not readily pass the blood-brain barrier due to its large size; concentration in the cerebrospinal fluid after an intravenous bolus is less than 10 per cent of plasma. Etoposide can be administered orally, by bolus intravenous infusion, or by continuous intravenous infusion over several days. Some authors report improved efficacy when etoposide is given by
Was this article helpful?