Following intravenous injection, etoposide has a biphasic clearance pattern with half-lives of 3 and 12 h. Both teniposide and etoposide are highly protein bound. Oral administration is characterized by marked intra-patient and interpatient variability, with 40–50% of either drug being absorbed. Epipodophyllotoxins also can inhibit nucleoside transport and impair incorporation of nucleosides into cellular nucleic acids. This is due to the inhibition of topoisomerase II, a nuclear enzyme responsible for the breakage and resealing of DNA. They are cell cycle specific, arresting cells at the S–G 2 interface and causing single strand breaks in DNA. II.B Mechanism of ActionĮpipodophyllotoxins differ from the parent podophyllotoxins, which inhibit microtubule formation due to the glucoside moiety on the C ring of the molecule. Chemical modification of podophyllotoxin by addition of the carbohydrate moieties β- d-thenylidene glucoside and β- d-ethylidene glucoside led to the development of teniposide and etoposide, respectively. Teniposide (VM-26) and etoposide (VP-16-213) are semisynthetic derivatives of podophyllotoxin, an extract of the mandrake plant ( Podophyllum peltatum). Weitberg, in Encyclopedia of Cancer (Second Edition), 2002 II Epipodophyllotoxins II.A Chemistry Peripheral neurotoxicity and hepatotoxicity are rare. Nausea, vomiting, and anorexia are common, as is alopecia, and rash. Toxicitiesĭose-limiting toxicity is myelosuppression, including leukopenia and thrombocytopenia, with nadir at 2 weeks, recovery at 3 weeks. Current indicationsĮtoposide is currently approved in the US as first-line treatment in SCLC (as a combination therapy with a platinum-based agent) and in refractory germ-cell tumors. Half-life is 6–8 h, and the drug is hepatically metabolized, with 40% renal excretion. Mechanism of actionĮtoposide inhibits topoisomerase II, thereby halting DNA transcription and cell division. Most of the published trials utilize infusional etoposide, but an oral formulation is available as well.Įtoposide is one of the most commonly used anti-cancer agents, as part of standard therapy for SCLC, leukemia/lymphoma, germ-cell tumors, and neuroblastoma. Also known as VP-16, this epipodophyllotoxin is used in SCLC and NSCLC, among many others. Rupard, in Encyclopedia of Respiratory Medicine, 2006 Etoposide (VePesid®, VP-16) OverviewĮtoposide is a semisynthetic derivative of podophyllotoxin, a substance found naturally in the mandrake plant. Resistance mechanisms include decreased expression of DNA topoisomerase II and the multidrugresistant (MDR) phenotype produced by increased expression of the p170 glycoprotein that increases drug efflux, decreasing intracellular accumulation. Etoposide poses an increased risk of secondary malignancies, particularly myelodysplasia and acute myelogenous leukemia associated with chromosome 11:23 translocations within 5 to 8 years of treatment. Adverse effects include myelosuppression, nausea/vomiting, anorexia, alopecia, mucositis, diarrhea, hypersensitivity reactions, fever, bronchospasm, dyspnea, hypotension, and radiation recall skin changes. Etoposide is indicated for the treatment of patients with germ cell tumors, lung cancer, Hodgkin's and non-Hodgkin's lymphomas, gastric cancer, breast cancer, and testicular cancer. Etoposide inhibits topoisomerase II by stabilizing the enzyme–DNA complex and preventing the unwinding of DNA. Gilman, in Cancer Immunotherapy, 2007 1 EtoposideĮtoposide is an alkaloid from the mandrake plant Podophyllum peltatum that has cell cycle-specific activity in the late S phase and G 2 phase.
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