Purpose: A phase 11 and pharmacokinetic study was designed to assess the efficacy and toxicity profile of an epidophyllotoxin analogue, GL331, in previously treated Chinese gastric cancer patients, with concurrent pharmacokinetic evaluation of the drug's metabolism. Material and methods: GL331 was given at 200 mg/m(2) as a daily 3-h infusion for 5 days every 4 weeks. Results: Enrolled in the study were 15 patients. One patient died from neutropenic sepsis before evaluation, one patient did not receive the full dose for reasons unrelated to GL331, nine patients had progressive disease with a median survival of 80 days, and five had stable disease with a median survival of 240 days. Grade 3 and 4 myelosuppression occurred in 10 of the 15 patients, with one death from neutropenic sepsis. This patient's peak GL331 concentration was 16.8 mug/ml,which was high compared to the mean peak drug concentration of 6 +/- 4.1 mug/ml. The mean systemic GL331 clearance was 12.1 +/- 7.2 l/h per m(2), much lower than 23.3 +/- 8.2 l/h per m(2) found in the phase I trial. Topoisomerase IIalpha was determined by immunohistochemistry and overexpression was detected in 3 of 11 specimens. Conclusions: GL331 was ineffective at this dose and schedule in this group of patients in spite of adequate blood levels of the drug.
