Phase II multicentre trial of ZD9331 monotherapy as first-line treatment for gastric cancer

Background ZD9331 is a novel, direct-acting and specific inhibitor of thymidylate synthase that has shown clinical activity and manageable tolerability in solid tumours. This phase II trial was designed to determine the antitumour activity and tolerability of ZD9331 given as a first-line therapy to patients with advanced gastric cancer. Patients and methods Eligible patients who were chemonaive with histologically or cytologically proven gastric cancer entered an open-label, multicentre, two-stage trial. Initially, patients were dosed at 130 mg/m(2) (Regimen 1); however, following a protocol amendment, the starting dose was reduced to 65 mg/m(2) (Regimen 2). Patients received ZD9331 as a 30-min i.v. infusion once weekly for 2 weeks followed by 1 week without treatment (3-week cycle). Results Twenty-nine patients with advanced, relapsed or inoperable gastric cancer were recruited from 11 centres across Europe. Five patients (17.2%), all from Regimen 2, showed a partial response and 16 patients (55.2%) had a best response of disease stabilisation. Most patients (72.4%) had a best response of disease control with median time to progression being 98 days. ZD9331 had manageable toxicity with the most frequently reported adverse events being neutropenia (62%) and diarrhoea (38%). Conclusions ZD9331, as a first-line treatment for patients with advanced gastric cancer, demonstrated clinical activity and manageable toxicity. (C) 2003 Lippincott Williams Wilkins.