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Pharmacodynamic Profile of Prolonged Etoposide Administration in Patients with Small Cell Lung Cancer and Non‐Hodgkin's Lymphoma
Author(s) -
Higa Gerald M.,
Sarkar Mohamadi A.,
DeVore Russell F.
Publication year - 1999
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.19.1.101.30508
Subject(s) - etoposide , medicine , pharmacodynamics , lung cancer , lymphoma , oncology , chemotherapy , pharmacokinetics
Study Objective. To determine whether therapeutic drug monitoring can enhance administration of etoposide in patients with drug‐responsive neoplasms. Design. Prospective, open‐label study. Setting. University‐affiliated hospital and cancer center. Patients. Sixteen patients with small cell lung cancer or low‐grade non‐Hodgkin's lymphoma. Interventions. Patients were treated with etoposide, 25 mg/m 2 /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°C until assayed. Measurements and Main Results. Steady‐state plasma etoposide concentrations (ECp ss ) were determined and used to calculate total systemic clearance (Cl sys ). Despite differences in dosage and administration schedules, etoposide Cl sys was similar to previous reports. In addition, a biexponential relationship between ECp ss and absolute neutrophil count was demonstrated by nonlinear least squares estimation. Values generated from this equation indicated that ECp ss above 1.5 μg/ml was strongly associated with grade III–IV leukocyte toxicity. Although less precise, there may also be a correlation between ECp ss and antitumor activity. Conclusion. Based on these findings, we propose a pharmacodynamic construct that uses measurements of both pharmacokinetic (ECp ss , Cl sys ) and pharmacodynamic (hematologic toxicity, tumor response) parameters for patients with etoposide‐sensitive tumors. Therapeutic drug monitoring may be able to mitigate hematologic toxicity.