Optimization of oral etoposide dosage in elderly patients with non-Hodgkin's lymphoma using the fraction of dose absorbed measured for each patient.

This study was undertaken to investigate the pharmacokinetics of etoposide for optimizing its oral dosage in elderly patients with non-Hodgkin's lymphoma (NHL) using the fraction of dose absorbed calculated from the data generated from first oral and intravenous doses in the same patient. Twenty-three NHL patients (ages 61-95 years) entered this study. Each received 50 mg/m2 of etoposide by 1-hour i.v. infusion, which was repeated every 24 hours for 5 days. The second cycle commenced on day 21, with etoposide being administered by mouth at a dose as close to 50 mg/m2 as possible. Serial blood samples were collected and analyzed for etoposide by HPLC. The fraction of dose absorbed (F) was calculated as F = (AUCor/AUCi.v.) (Di.v./Dor), and etoposide was then given orally for the following 20 days at a daily dose equivalent to Dor/F. After 1 week free of etoposide administration, a second cycle of oral etoposide at the adjusted dose was given for 21 days. The mean +/- SD values for t1/2 beta, tmax, Cmax, CLTor, and MRT observed following the first oral dose were 8.98 +/- 4.84 h, 1.39 +/- 0.96 h, 0.083 +/- 0.046 mg.L-1/mg.m-2, 1.89 +/- 1.2 L.h-1/m2, and 10.37 +/- 2.76 h, respectively, and those observed following the first intravenous dose were 8.05 +/- 5.11 h, 1.57 +/- 0.17 h, 0.142 +/- 0.043 mg.L-1/mg.m-2, 1.25 +/- 0.44 L.h-1/m2, and 7.69 +/- 1.53 h, respectively. The mean +/- SD of F was 0.80 +/- 0.34. The data obtained indicate that optimization of etoposide oral dosage using F yielded good clinical results while keeping the morbidity at a level that is similar to that of the i.v. administration.