Phase I trial of fixed dose rate infusion (FDRI) gemcitabine (GEM) with gefitinib in patients with advanced pancreatic carcinoma

4118 Background: Patients (pts) with metastatic pancreatic adenocarcinoma (PCa) treated with GEM using a FDRI have a longer survival than with 30 min infusion schedules1. Over 40% of metastatic PCa’s overexpress EGFR2. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of GEM using a FDRI in combination with gefitinib, an EGFR TK inhibitor in pts with PCa. Methods: Pts with advanced pancreatic cancer were given GEM at the FDRI of 10 mg/m2/min IV on days 1, 8, and 15 of a 28 day cycle. Dose levels of 1000, 1200 and 1500 mg/m2 were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as two instances of grade III hematologic or IV non-hematologic toxicity or any grade IV hematologic toxicity. Four pts were treated at each dose level. Dose level escalation occurred in the absence of DLTs. Results: Four women and 8 men were enrolled. Median age was 61. All pts were PS 0 or 1 and had metastatic disease (83.3% liver; 16.6% lungs). Three pts received...