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/m(2)/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 (C-24) to achieve a target concentration of 1.5 mu g/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 mu g/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 mu g/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35 +/- 6 mg/m(2) daily. The C-24 was 1.8 +/- 0.4 mu g/ml and ranged from 1.1 to 2.9 mu g/ml. Following dose modification, the mean concentration from 96 to 336 h (C-mean) was 1.6 +/- 0.2 mu g/ml and ranged from 1.2 to 2.0 mu g/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.