Phase I study of gemcitabine (GEM) and premetrexed (ptx) in the treatment of advanced solid tumors

12025 Background: GEM has activity against a wide range of tumors and ptx is a multitargeted antifolate agent with activity in mesothelioma and non small lung cancer (NSCLC). A phase I study of a combination of GEM plus ptx for advanced malignancies was conducted. Methods: Patients with advanced malignancies were enrolled in this accelerated dose escalation trial. Both patients with or without prior chemotherapy were also eligible. They were treated with Gem followed by ptx on days 1 and 15 every 4 weeks. The starting dose was GEM 1250 mg/m2 and ptx 300 mg/m2. The dose of each drug was escalated alternately by 250 mg for GEM and 50 mg for ptx at each dose level. Results: A total of 41 patients (9 female/32 males) with median age of 60 years were enrolled at 6 dose levels. A total of 93 cycles were conducted with a median number of 2 cycles/pt. 35 patients were assessable for efficacy and all courses were assessable for toxicity. Grade 3/4 neutropenia was observed in 8 cycles whereas grade 3 /4 anemia and ...