5 research outputs found
A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin)
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