DOSING OF ORAL ETOPOSIDE NORMALIZED FOR BODY-SURFACE AREA

The objective of this clinical and pharmacological study was to determ ine whether any pretreatment parameters were associated with pharmacol ogical or toxicity parameters after prolonged oral etoposide. Therefor e, the relationships between patient characteristics and etoposide con centrations and hematological toxicity were evaluated. Sixty patients with advanced non-small cell lung cancer were treated with etoposide 5 0 mg/m(2)/day p.o. for 21 consecutive days and cisplatin 100 mg/m(2) i .v. on day 1. Complete blood counts and etoposide plasma concentration s were obtained weekly. Etoposide was measured by high-performance liq uid chromatography. The input variables were age, gender, race, weight , weight(0.66), weight(0.75), height, body surface area, performance s tatus, albumin concentration, and total etoposide dose. The outcome me asures were,etoposide concentration; nadir values (white blood cells, neutrophils, hemoglobin, and platelets); the absolute decrease, relati ve decrease, and survival fraction of blood cells; and graded toxicity . No significant correlations were found in 49 fully evaluable patient s between any of the input and outcome variables. Among the outcome va riables, significant correlations were found between etoposide concent ration and the logarithmic transformation of the nadir blood counts. I f any of the input variables were significantly correlated to etoposid e concentrations or toxicity variables, it would be possible to sugges t another predictor variable besides body surface area. As long as tre atment is not modified for etoposide concentrations, dosing of oral et oposide must still rely on estimates of body surface area.