Prolonged exposure to topotecan in in vitro and in vivo experiments has
yielded the highest antitumor efficacy. An oral formulation of topotecan
with a bioavailability of 32-44% in humans enables convenient prolonged
administration. Pharmacokinetic/pharmacodynamic relationships from four
Phase I studies with different schedules of administration of oral
topotecan in 99 adult patients with malignant solid tumors refractory to
standard forms of chemotherapy were compared. Topotecan was administered
as follows: (a) once daily (o.d.) for 5 days every 21 days (29 patients);
(b) o.d. for 10 days every 21 days (19 patients); (c) twice daily (b.i.d.)
for 10 days every 21 days (20 patients); and (d) b.i.d. for 21 days every
28 days (31 patients). Pharmacokinetic analysis was performed in 55
patients using a validated high-performance liquid chromatographic assay
and noncompartmental pharmacokinetic me