Phase I Study Of High-Dose Bi-Weekly Gemcitabine At A Constant Rate Infusion (Cri) Without Growth Factor Support In Advanced Solid Tumors, Including Prior Standard Gemcitabine Treated Patients.

2067 Background:Phosphorylation of gemcitabine by deoxycytidine kinase is the rate-limiting step in the accumulation of the active triphosphate metabolite. This enzyme is saturable and the optimal infusion dose rate that maximizes amount of gemcitabine triphosphate is 10 mg/m2/min. Previous experience of weekly gemcitabine at this CRI produced a maximum tolerated dose (MTD) close to the already recommended 30-minute infusion. We are investigating the MTD of gemcitabine at a CRI in patients with solid tumors using a biweekly regimen. Methods: Metastatic patients failing standard therapy (1 or no prior chemotherapy including standard 30-minute gemcitabine) were eligible. Gemcitabine was infused at a CRI of 10 mg/m2/minute every 2 weeks starting at 2,400 mg/m2 with 9 predefined dose-level (DL). In the absence of dose-limiting toxicity (DLT) dose was increased 600 mg/m2 at each DL. Results: Twenty patients (6 female, 14 male); median age 54 (range 38–74); ECOG 0 (10), 1 (10); diagnoses: cholangiocarcinoma (3)...