Chronic etoposide administration: overview of clinical experience

Etoposide is an important anti-neoplastic drug, but the best dose and schedule for its administration remain unknown. The schedule-dependency of etoposide for small cell lung cancer (SCLC) is now proven and it is probably true for other sensitive neoplasms as well (e.g., lymphoma and germ cell tumors). Recent data suggest that an extended schedule of administration (i.e., 14 to 21 days) may be more effective than the standard 3- to 5-day schedule. Several phase II studies with etoposide have demonstrated its activity against several neoplasms. Some have assessed the relationship of etoposide plasma levels to dose, schedule, and tumor responsiveness. Preliminary data suggest that high peak plasma levels (i.e., > 5 to 10 micrograms/ml) are associated with more severe myelosuppression than lower peak plasma levels (i.e., 1 to 3 micrograms/ml). Response and survival rates in previously untreated SCLC patients given low daily doses of etoposide for 14 to 21 days are at least comparable with results achieved with standard etoposide doses given for 3 to 5 days, and the extended etoposide schedule is less toxic than the 3- to 5-day schedule. Preliminary data from several studies suggest that administering low, daily etoposide doses over a prolonged schedule is a superior method of administration. Other studies, including randomized comparisons, are necessary to confirm these observations.