Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma.

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine using a fixed dose rate infusion (FDRI) in combination with gefitinib in patients (pts) with pancreatic adenocarcinoma (PCa). Patients and methods: Patients with advanced PCa were given gemcitabine 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 2 instances of Grade 3 hematologic or 4 nonhematologic or any Grade 4 hematologic toxicity. At least 4 patients were treated at each dose level. Dose escalation occurred in the absence of DLTs. Results: Five women and 8 men were enrolled. Median age was 59 and performance status 1. All had metastatic disease. Four patients received prior adjuvant chemoradiation for PCa, and one chemotherapy for lung cancer. Median cycles were 4 per patient. The MTD was 1,200 mg/m2. Toxicity was predominantly hematologic. At 1,500 mg/m2, 1...