Trial Information

Pharmacokinetics of Etoposide in Patients With Breast Cancer Receiving High-Dose Etoposide

Etoposide is a topoisomerase II inhibitor that has a broad range of anticancer activity at
conventional doses (100 mg/m(2) daily x 5 days) and is administered in high doses (greater
than 1200 mg/m(2)) as a component of pre-transplant myeloablative chemotherapy regimens.
Etoposide pharmacokinetics are linear over a 30-fold dose range, but disposition is highly
variable. Etoposide is highly protein bound (95%) to albumin, but protein binding (and
therefore free drug concentrations) vary widely in cancer patients. Etoposide is eliminated
by metabolism and renal excretion, which may also contribute to the variability. The
pharmacokinetics of etoposide will be studied in patients receiving high-dose etoposide as
part of their pre-transplant preparative regimen, and pharmacokinetic parameters generated
from pharmacokinetic modeling will be correlated with clinical and laboratory
characteristics and toxicity in order to develop more rational dosing methods.