Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

LoRusso, P.M. et al.

Patricia M. LoRusso, Shirish M. Gadgeel, Antoinette Wozniak, Alan J. Barge, Helen K. Jones, Zachary S. DelProposto, Pamela A. DeLuca, Jeffrey L. Evelhoch, Scott A. Boerner, Catherine Wheeler,

Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors.

BACKGROUND: ZD6126 is a novel vascular-targeting agent that disrupts the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor necrosis. This Phase I clinical study was conducted to evaluate the dose and administration schedule of ZD6126. METHODS: Adult patients with solid tumors refractory to existing treatments received a 10-min, single-dose intravenous infusion of ZD6126 every 14 or 21 days. Subsequent dose escalation was performed, based on the incidence of adverse events (AEs) within the first cycle of drug administration. Blood samples were obtained for pharmacokinetic analysis, and the effects of ZD6126 on tumor vasculature were visualized using DCE-MRI technology. RESULTS: Forty-four patients received ZD6126 (5-112 mg/m2 in the 21-day schedule, n=35; 40-80 mg/m2 in the 14-day schedule, n=9). Common AEs were similar in both groups and included abdominal pain, nausea and vomiting, which appeared to be dose related. The incidence of abdominal pain at 112 mg/m2 in the 21-day study prevented further dose escalation. Pharmacokinetic studies confirmed that ZD6126 is rapidly hydrolyzed to ZD6126 phenol. There was no difference in the pharmacokinetics of ZD6126 phenol upon repeat administration or between the two dosing regimens. DCE-MRI evaluation has demonstrated the antivascular effects of ZD6126. CONCLUSIONS: This study identified that ZD6126 administered every 2 or 3 weeks at 80 mg/m2 was well tolerated, with mild but manageable gastrointestinal AEs. In approximately 11% (5 out of 44) of patients, ZD6126 was associated with cardiac events categorized as dose limiting toxicities (one patient with asymptomatic decreased left ventricular ejection fraction (LVEF), two with increased troponin concentrations, one with myocardial ischemia, and one with ECG signs of myocardial ischemia).[1]

References

Phase I clinical evaluation of ZD6126, a novel vascular-targeting agent, in patients with solid tumors. LoRusso, P.M., Gadgeel, S.M., Wozniak, A., Barge, A.J., Jones, H.K., DelProposto, Z.S., DeLuca, P.A., Evelhoch, J.L., Boerner, S.A., Wheeler, C. Invest. New. Drugs (2008) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.