Gemcitabine in patients with solid tumors and renal impairment - A Pharmacokinetic Phase I Study

The purpose of this phase 1 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-Cr-51 plasma clearance (CLp, mL/min): greater than or equal to80; greater than or equal to60 and <80; greater than or equal to30 and <60; and greater than or equal to30 and <80 plus renal insufficiency induced by previous chemotherapy, respectively. Gemcitabine 500 to 1000 mg/m(2) 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 CLp and indices of renal impairment (EDTA-Cr-51 Cr-51 CL; p = 0.797 or beta(2)-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.