Prolonged administration of low-daily-dose etoposide: a superior dosing schedule?

Despite the clinical use of etoposide for about 20 years, the best dose and schedule of administration remains unknown. The schedule dependency for small-cell lung cancer (SCLC) has been unequivocally demonstrated, and it is probably similar for other sensitive neoplasms (for example, lymphoma, germ cell tumors). A more extended schedule of administration (i.e., 14-21 days) may be more effective than the standard 3- to 5-day schedule. Plasma levels in reference to dose, schedule, and tumor responsiveness have been evaluated in several studies. These data suggest that high peak levels (i.e., > 5-10 micrograms/ml) are most often associated with more severe myelosuppression than are lower peak plasma levels (i.e., 1-3 micrograms/ml). In SCLC patients the response rates and survival observed following the administration of low daily etoposide doses for 14-21 days are similar to the results achieved with standard doses given for 3-5 days. These data as well as other studies suggest that giving low daily doses of etoposide on a prolonged schedule is superior. Randomized comparisons are necessary for an unequivocal confirmation of these observations.