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 μg/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 (Cbefore). 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 Cbefore of 1.7±0.1 (μg/ml, mean±SE) was decreased to 1.3±0.2 after day 5 (Cafter). Among 7 courses with dose escalation, the Cbefore of 0.9±0.0 was increased to the Cafter of 1.2±0.1. Among the remaining 12 courses without dose modification, the Cbefore and the Cafter 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.