Clinical pharmacological profile of etoposide in elderly patients with lung cancer

To clarify the clinical pharmacological profile of etoposide in the elderly, we carried out prospective therapeutic drug monitoring in 14 patients with advanced lung cancer aged 75 or more years. The patients received 50 mg etoposide as oral capsules for 21 consecutive days during the first course, and intravenous etoposide for 3 days during the second course of palliative treatment. Plasma and urine samples were collected on days 1 and 21 of the first course and day 1 of the second course, and etoposide concentrations were measured using high‐performance liquid chromatography. We compared these data with those obtained from 17 adult patients under 75 years old who participated in our previous study of combined oral etoposide/carboplatin chemotherapy. Within the elderly group, no significant differences in the area under the concentration‐versus‐time curve, elimination half‐life, plasma clearance, urinary excretion or bioavailability of oral etoposide were observed between day 1 and day 21. However, the mean (±SD) elimination half‐lives for elderly and adult patients were 10.3 ± 1.9 h and 5.8 ± 2.5 h, respectively, while the mean (±SD) bioavailabilities were 62.8 ± 27.5% and 37.4 ± 15.4%; both were significantly increased in the elderly patients. Our previously proposed limited sampling model was validated using the elderly data set and proved to be unbiased and precise. In conclusion, although no accumulation of oral etoposide was observed in elderly patients, there were age‐dependent changes in its pharmacokinetics, especially in bioavailability.