Eight patients with non-small cell lung cancer were given long-term oral therapy with lowdose etoposide (25mg to 5 patients and 50mg to 3), and the pharmacokinetics, efficacy, and safety were evaluated to determine the optimal administration method.
Blood was collected 7-10 times on the day when treatment was initiated, and periodically thereafter for up to 60 days to measure the plasma etoposide concentration. The data obtained at each time on the initial day were analyzed and the pharmacokinetic parameters for each patient were calculated by the Bayesian method to estimate the plasma levels on day 2, 7, 14, 30, and 60 of treatment. The estimated levels conformed well to the actual measured data, and it was hence judged that no accumulation of the drug occurred during long-term therapy. No toxity (including hematological toxity) that required the discontinuation of treatment occurred, suggesting that the maximum tolerable dose (MTD) was not reached.
Administration of a daily dose of 25mg did not maintain a sufficient plasma concentration, and not less than 50mg/day seemed to be needed. In view of the necessity for increasing the duration of a plasma level of ≥1μg/ml, treatment with a daily dose of 75 mg divided into 3 portions appears to be worth considering.
