Therapeutic Drug Monitoring of Etoposide in a 14-Day Infusion for Non-small-cell Lung Cancer

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/m2day 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 μg/ml. We postulated that severe toxicities could be avoided by maintaining the steady‐state concentration at less than 2 7mu;g/ml, while antitumor activity could be expected if the steady‐state concentration was maintained at more than 1 μg/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 μg/ml and ranged from 1.1 to 2.9 μg/ml. Following dose modification, the mean concentration from 96 to 336 h (Cmean) was 1.6±0.2 μg/ml and ranged from 1.2 to 2.0 μg/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.