RANDOMIZED COMPARISON OF ETOPOSIDE PHARMACOKINETICS AFTER ORAL ETOPOSIDE PHOSPHATE AND ORAL ETOPOSIDE

Etoposide phosphate is a water-soluble prodrug of etoposide. The plasm a pharmacokinetics of etoposide following oral administration of etopo side phosphate or oral etoposide were compared. Seventeen patients wit h solid tumours were enrolled to receive oral etoposide phosphate 125 mg m(-2) on days 1-5 every 3 weeks, with escalation to 175 mg m(-2) fr om course 3 when possible. Patients were randomized to receive oral et oposide phosphate or oral etoposide on day 1 of course 1 and the alter native compound on day 1 of course 2. Fifteen patients received two or more courses and were evaluable for pharmacokinetic comparisons. The median AUC(inf) (area under the concentration vs time curve from zero to infinity) of etoposide was 77.7 mg l(-1) h after etoposide phosphat e (95% CI 61.3-100.5) and 62.0 mg l(-1) h after oral etoposide (95% CI 52.2-76.9). The difference in favour of etoposide phosphate was borde rline significant: median 9.9 mg l(-1) h (95% CI 0.1-32.8 mg l(-1) h; P = 0.05). However, the inter-patient variability of etoposide AUC(inf ) was not improved (coefficients of variation 42.3% and 48.4%). Etopos ide phosphate was undetectable in plasma after oral administration. To xicities of oral etoposide phosphate were not different from those kno wn for etoposide. In conclusion, oral etoposide phosphate does not off er a clinically relevant benefit over oral etoposide.