Abstract
To determine whether therapeutic drug monitoring can enhance administration of etoposide in patients with drug-responsive neoplasms. Prospective, open-label study. University-affiliated hospital and cancer center. Sixteen patients with small cell lung cancer or low-grade non-Hodgkin's lymphoma. Patients were treated with etoposide, 25 mg/m2/day over 24 hours by continuous infusion for 35 days. Peripheral blood samples were collected twice a week to measure etoposide levels. Plasma was separated, frozen and stored at -20 degrees C until assayed. Steady-state plasma etoposide concentrations (ECpss) were determined and used to calculate total systemic clearance (Clsys). Despite differences in dosage and administration schedules, etoposide Clsys was similar to previous reports. In addition, a biexponential relationship between ECpss and absolute neutrophil count was demonstrated by nonlinear least squares estimation. Values generated from this equation indicated that ECpss above 1.5 microg/ml was strongly associated with grade III-IV leukocyte toxicity. Although less precise, there may also be a correlation between ECpss and antitumor activity. Based on these findings, we propose a pharmacodynamic construct that uses measurements of both pharmacokinetic (ECpss, Clsys) and pharmacodynamic (hematologic toxicity, tumor response) parameters for patients with etoposide-sensitive tumors. Therapeutic drug monitoring may be able to mitigate hematologic toxicity.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call