A phase I and pharmacokinetic study of liposomal vinorelbine in patients with advanced solid tumor
Journal
Investigational New Drugs
Journal Volume
30
Journal Issue
1
Pages
282-289
Date Issued
2012
Author(s)
Abstract
Purpose This phase I study was performed to determine the maximum tolerated dose (MTD) and doselimiting toxicity (DLT) of an untargeted liposomal formulation of vinorelbine (NanoVNB?) and to characterize its plasma pharmacokinetics in patients with advanced solid tumors which were refractory to conventional treatment or without an effective treatment. Patients & methods The study incorporated an accelerated titration design. Twentytwo patients with various solid tumors were enrolled. NanoVNB? was administered intravenously at doses of 2.2-23 mg/m 2 once every 14 days. Pharmacokinetic endpoints were evaluated in the first cycle. The safety profiles and anti-tumor effects of NanoVNB? were also determined. Results Skin rash was the DLT and the most common non-hematological toxicity. The MTD was 18.5 mg/m 2. Drug-related grade 3-4 hematological toxicities were infrequent. Compared with intravenous free vinorelbine, NanoVNB? showed a high Cmax and low plasma clearance. Of the 11 patients completing at least 1 post-treatment tumor assessment, 5 had stable disease. No responders were noted. Conclusion NanoVNB? was well tolerated and exhibited more favorable pharmacokinetic profiles than free vinorelbine. Based on dose-limiting skin toxicity, further evaluation of NanoVNB? starting from 18.5 mg/m 2 as a single agent or in combination with other chemotherapeutic agents for vinorelbine-active malignancies is warranted. ? Springer Science+Business Media, LLC 2010.
SDGs
Other Subjects
liposome; nanovnb; navelbine; unclassified drug; acne; adult; advanced cancer; aged; anemia; anorexia; antineoplastic activity; area under the curve; article; ataxia; clinical article; controlled study; dose response; drug distribution; drug dose escalation; drug formulation; drug half life; drug tolerability; female; gastrointestinal hemorrhage; glossitis; human; leukopenia; liposomal delivery; malaise; male; maximum plasma concentration; maximum tolerated dose; mean residence time; multiple cycle treatment; phase 1 clinical trial; plasma clearance; priority journal; rash; side effect; skin ulcer; solid tumor; syncope; weight reduction; Adult; Aged; Analysis of Variance; Antineoplastic Agents, Phytogenic; Area Under Curve; Female; Half-Life; Humans; Infusions, Intravenous; Liposomes; Male; Maximum Tolerated Dose; Metabolic Clearance Rate; Middle Aged; Neoplasms; Taiwan; Treatment Outcome; Vinblastine
Type
journal article