title: Therapeutic drug monitoring of etoposide in a 14-day infusion for non-small-cell lung cancer.
abstract: We investigated whether a constant plasma concentration could be obtained by the individualized administration of low-dose, prolonged-infusional etoposide. Etoposide was infused for 14 days at 40 mg/m2/day initially in patients with inoperable non-small-cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C24) to achieve a target concentration of 1.5 microgram/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 microgram/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 microgram/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35+/-6 mg/m2 daily. The C24 was 1.8+/-0.4 microgram/ml and ranged from 1.1 to 2.9 microgram/ml. Following dose modification, the mean concentration from 96 to 336 h (C mean) was 1.6+/-0.2 microgram/ml and ranged from 1.2 to 2.0 microgram/ml. The toxicities were well-tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment-related deaths. Following dose modification, the inter-patient variability was decreased successfully. Although this pharmacologically-guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: H
authors.initials: H
authors.lastname: Minami
authors.forename: H
authors.initials: H
authors.lastname: Saka
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: S
authors.initials: S
authors.lastname: Sakai
authors.forename: K
authors.initials: K
authors.lastname: Shimokata
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide