Etoposide and
teniposide are closely related derivatives of
podophyllotoxin, and both have a phase-specific action in the late S and early G2 phases of the cell cycle.
Etoposide has attracted more widespread use and study, although no evidence suggests a differing mode of action or spectrum of anticancer activity. The drugs have significant differences in their clinical pharmacology, however.
Teniposide exhibits greater protein-binding affinity, has a longer plasma terminal elimination half-life, and has reduced plasma and renal clearances. Little is accurately known about the metabolism of either
drug, but the fact that 40% to 60% of administered
etoposide is accounted for by excretion or metabolism, whereas the range is only 10% to 25% for
teniposide, reflects a further difference between the drugs. Renal dysfunction impairs
etoposide excretion, but the effect of hepatic impairment on drug clearance is unclear. A specific oral formulation exists only for
etoposide, although the unpalatable intravenous preparations of both drugs can be taken orally. The bioavailability of oral
etoposide is about 50% at doses of 200 mg or less and decreases as
drug doses increase. There is considerable intrapatient and interpatient variation in
etoposide absorption, but the reasons for this are unknown. In vitro, the efficacy of
etoposide is highly dependent on the schedule of administration. The superior efficacy without increased toxicity of more prolonged schedules of
etoposide administration has been demonstrated recently in patients with
small cell lung cancer (SCLC). Although the optimal schedule in any specific
tumor is not known, current pharmacodynamic evidence suggests that the efficacy of
etoposide, at least in SCLC, is related to the maintenance of prolonged low blood concentrations of
drug.