Therapeutic drug monitoring in 21-day oral etoposide treatment for lung cancer

We aimed to determine whether or not therapeutic drug monitoring is applicable to 21-day oral etoposide treatment for lung cancer. As the starting dose, a 25-mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 mu g/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (C-before). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the C-before of 1.7 +/- 0.1 (mu g/ml, mean +/- SE) was decreased to 1.3 +/- 0.2 after day 5 (C-after). Among 7 courses with dose escalation, the C-before of 0.9 +/- 0.0 was increased to the C-after of 1.2 +/- 0.1. Among the remaining 12 courses without dose modification, the C-before and the C-after were 1.2 +/- 0.0 and 1.3 +/- 0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.