The activity of 10-, 14-, and 21-day schedules of single-agent etoposide in previously untreated patients with extensive small cell lung cancer.

Pharmacologic studies in patients with small cell lung cancer treated with differing schedules of intravenous etoposide over 1 to 8 days have suggested that etoposide's antitumor cytotoxicity is related to duration of exposure to low plasma levels of drug. Three phase II studies have been performed in 78 patients with extensive small cell lung cancer examining the efficacy and toxicity of 50-mg doses of oral etoposide given twice daily for 14 days every 3 weeks, once daily for 21 days every 4 weeks, and twice daily for 10 days every 3 weeks. Partial response rates were observed in 76%, 52%, and 70% of patients, respectively. Median response duration appeared similar in all three schedules, but the time to achieve a response appeared longer in the 21-day, once-daily schedule. Bone marrow toxicity was generally mild, but occasionally severe nadir blood counts were observed. These studies demonstrate that prolonged administration of low-dose oral etoposide is very active in small cell lung cancer, and that a twice-daily regimen is preferable in view of the greater rapidity of response and possibly higher response rate. The optimal duration of a twice-daily, 50-mg dosage schedule remains to be determined.