Phase II Study Evaluating the Effect of Concomitant Ramucirumab on the Pharmacokinetics of Docetaxel in Patients with Advanced Solid Tumors
- Corresponding Author:
- Stein MN
Rutgers Cancer Institute of New Jersey
195 Little Albany Street New Brunswick, NJ, USA
E-mail: [email protected]
Received Date: July 20, 2016; Accepted Date: August 31, 2016; Published Date: September 06, 2016
Citation: Stein MN, Chow LQM, Smith DC, Shepard DR, Wang D, et al. (2016) Phase II Study Evaluating the Effect of Concomitant Ramucirumab on the Pharmacokinetics of Docetaxel in Patients with Advanced Solid Tumors. Clin Pharmacol Biopharm 5:161. doi: 10.4172/2167-065X.1000161
Copyright: © 2016 Stein MN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Ramucirumab is a human IgG1 monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2. The primary objective of this study was to investigate the effect of concomitant ramucirumab on the pharmacokinetics of docetaxel. Methods: Patients with metastatic or locally advanced malignant solid tumors resistant to standard therapy or for which no standard therapy was available were recruited. Patients received docetaxel 75 mg/m2 and ramucirumab 10 mg/kg on day 1 of a 3-week cycle. In cycle 1, docetaxel was administered alone; in cycle 2 and subsequent cycles, ramucirumab was administered followed by docetaxel. Blood was drawn immediately before and at regular intervals after infusions for cycles 1 and 2 to determine docetaxel and ramucirumab concentrations. Results: Docetaxel pharmacokinetic parameters were assessed in 18 patients. The dose-normalized area under the plasma concentration versus time curve from time zero extrapolated to infinity and maximum plasma drug concentration of docetaxel during cycle 2 were similar to those when docetaxel was administered alone during cycle 1, with geometric least squares means ratios of 0.97 (90% CI: 0.84, 1.10) for the area under the plasma concentration versus time curve from time zero extrapolated to infinity and 1.14 (90% CI: 0.84, 1.55) for the maximum plasma drug concentration. Of the 22 patients who received any dose of study drug, the most commonly reported treatment-emergent adverse events included nausea (12 patients, 54.5%), fatigue, leukopenia, and neutropenia (each in nine patients, 40.9%). The most commonly reported grade ≥ 3 treatment-emergent adverse events were leukopenia and neutropenia (each in seven patients, 31.8%). Conclusions: Coadministration of ramucirumab had no effect on the pharmacokinetics of docetaxel. The incidence and severity of treatment-emergent adverse events were consistent with the known safety profiles of docetaxel and ramucirumab.