Chronic daily administration of oral etoposide

Etoposide is a useful antineoplastic drug, but its optimal dose and schedule of administration remain unknown. In small cell lung cancer (SCLC), an intravenous dose given on a 5-day schedule is clearly superior to the same dose given over 1 day. The standard dose has been in the range of 300 to 500 mg/m2 divided over 3 to 5 days. Whether this schedule dependency (superiority) extends beyond 5 days is unknown. We have investigated patients with several refractory neoplasms who were given oral etoposide over a long-term period (21-day cycles) in a phase 1 trial. The maximum tolerated dose is 50 mg/m2/d for 21 days. The major toxicity is myelosuppression, which usually resolves by days 28 to 35. Responses were seen in several patients. Phase II trials are under way, and it appears that the long-term daily administration of etoposide is more active than the standard schedule. Responses have been seen in refractory germ cell tumors, lymphomas, and SCLC in patients who have progressed on the standard dose and schedule of etoposide. In addition, the drug may be active in soft tissue sarcoma. Preliminary results of combination chemotherapy with cisplatin show good tolerance and activity. The long-term daily administration of etoposide may prove to be a superior schedule and, as such, may be incorporated into combination chemotherapy for several neoplasms.