Phase I study of imatinib, cisplatin, and fluoruracil in patients with advanced gastric cancer.

115 Background: Combination chemotherapies are established as standard treatment in gastric cancer, but prognosis remains poor. Integration of targeted therapies may provide an additional benefit. Imatinib may inhibit platelet derived growth factor (PDGF) mediated tumor growth and amplify effects of chemotherapy. This Phase I study evaluated dose limiting toxicity (DLT) of imatinib in combination with cisplatin and fluoruracil/ capecitabine therapy in gastric cancer. Methods: The study was designed as a 3-patient cohort dose-escalating trial. Patients (pts) received cisplatin (60 mg/m2 d1 q 21) and capecitabine (1250 mg/m2 bid d1-14 q 21) or cisplatin (50 mg/m2 d1, 15, 29 q 50) and leucovorin (500 mg/m2), followed by a 24-hour 5-fluoruracil infusion (2000 mg/m2 d1,8,15,22,29,36 q 50). Imatinib was started d - 4 and continuously administered with the dose being escalated from 300 to 700 mg QD in 100 mg steps. Results: Characteristics of the 35 enrolled pts: Median age= 61 years (range 39-76). Male: female=...