The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and pharmacodynamics of
etoposide are reviewed.
Etoposide, although similar in chemical structure to
podophyllotoxin, has a different mechanism of cytotoxicity compared with its parent compound.
Etoposide may stabilize type II topoisomerase-
DNA complexes, preventing rejoining of single- and double-strand DNA breaks.
Etoposide may also require cellular activation into intermediates, which then bind to
DNA and disrupt cellular function. Oral
etoposide has an average bioavailability of 50% (range, 17%-137%), with substantial intrapatient and interpatient variability.
Etoposide is widely distributed in the body and is highly bound to
plasma proteins (greater than 95%). Approximately 50% (range, 20%-81%) of an
etoposide dose is recovered in the urine as parent
drug or
glucuronide, with the remainder of the dose being unaccounted for. The disposition of
etoposide in patients with renal and hepatic dysfunction is discussed.
Etoposide is effective in combination with other agents against
lung cancer, and response rates of 90% in
small-cell lung cancer have been observed. When
etoposide is used in combination with other agents, response rates of approximately 80% have been observed in patients with
testicular cancer. The activity of
etoposide in treating
leukemia,
lymphoma, and breast and ovarian
carcinomas and other
tumors is discussed. The impact of
etoposide on prolonging survival in lung and
testicular cancer is addressed, and studies evaluating the pharmacodynamics of
etoposide are described. Adverse effects associated with
etoposide therapy include myelosuppression,
alopecia,
nausea and
vomiting,
mucositis, and
hypotension after rapid
intravenous administration.
Etoposide has demonstrated considerable clinical efficacy against a broad spectrum of
tumors.