Gemcitabine in patients with solid tumors and renal impairment: A pharmacokinetic phase I study

The purpose of this phase I study was to determine the pharmacokinetics and toxicity of gemcitabine in patients with advanced, recurrent, and/or metastatic cancer and renal impairment. Patients were entered in 4 groups estimated by EDTA-Cr⁵¹ plasma clearance (CL_p, mL/min): ≥80; ≥60 and <80; ≥30 and <60; and ≥30 and <80 plus renal insufficiency induced by previous chemotherapy, respectively. Gemcitabine 500 to 1000 mg/m² was administered intravenously on days 1, 8, and 15 every 4 weeks. Plasma concentration data were pooled and analyzed using a population pharmacokinetic program (NONMEM). Eighteen white patients (14 females, 4 males) entered the study with a median age of 55 years. Linear regression analyses revealed no significant relationship between gemcitabine CL_p and indices of renal impairment (EDTA-Cr⁵¹ CL; p = 0.797 or β₂-microglobulin; p = 0.153). Hematologic and nonhematologic toxicities were mild. Thus, there seems to be no significant impact of mild to moderate renal insufficiency on gemcitabine pharmacokinetics in patients with advanced cancer.