Pharmacokinetics and toxicity of the epipodophyllotoxin derivative etoposide (VP 16-213) in patients with gestational choriocarcinoma and malignant teratoma.

Serum levels of etoposide obtained 5 min after administration of 100 mg/m2 were between 11 and 30 micrograms/ml. By 24 h after drug administration, serum levels had fallen to between 0.19 and 1.11 micrograms/ml. Interpatient variation of etoposide serum concentrations obtained 5 min after drug administration was low, whereas interpatient variation 24 h later was noticeably higher. A significant correlation was observed (r = -0.698) between the WBC nadir and the mean etoposide serum concentrations, measured 24 h after drug administration, in patients receiving etoposide in combination with cyclophosphamide and actinomycin D. However, a relationship was not observed in those patients receiving etoposide alone. There was no observed difference in the efficacy or toxicity of 500 mg/m2 etoposide when the dose was administered either as 100 mg/m2 on each of 5 consecutive days or as 250 mg/m2 on days 1 and 3. There was no significant difference between AUC values calculated from etoposide concentration versus time profiles in patients receiving the drug on days 1 and 3 and those values obtained with the 5-day schedule. Patients resistant to a conventional dose of etoposide were given a higher dose of 1 g/m2/24 h, but this schedule did not cause an increase in efficacy despite an increase in serum levels of the drug. CSF levels in two of these patients receiving high-dose etoposide were 1.28% and 2.09% of the serum concentrations.