Imperial College London
Portrait Picture

ProfessorPatriciaPrice

Faculty of Medicine, Department of Surgery & Cancer

Visiting Professor
 
 
 
//

Contact

 

p.price

 
 
//

Location

 

BN1/24 B BlockHammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Patterson:2012:10.1158/1078-0432.CCR-11-2414,
author = {Patterson, DM and Zweifel, M and Middleton, MR and Price, PM and Folkes, LK and Stratford, MR and Ross, P and Halford, S and Peters, J and Balkissoon, J and Chaplin, DJ and Padhani, AR and Rustin, GJ},
doi = {10.1158/1078-0432.CCR-11-2414},
journal = {Clin Cancer Res},
pages = {1415--1425},
title = {Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors},
url = {http://dx.doi.org/10.1158/1078-0432.CCR-11-2414},
volume = {18},
year = {2012}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PURPOSE: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents. EXPERIMENTAL DESIGN: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors. RESULTS: Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m(2), then expanded cohorts to 15.4 mg/m(2) in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m(2) or higher. CONCLUSIONS: The maximum tolerated dose was 8.5 mg/m(2) but escalation to 14 mg/m(2) was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m(2) and maximum tumor perfusion reductions were seen at doses of 11 mg/m(2) or higher, the recommended phase II dose is from 11 to 14 mg/m(2).
AU  - Patterson,DM
AU  - Zweifel,M
AU  - Middleton,MR
AU  - Price,PM
AU  - Folkes,LK
AU  - Stratford,MR
AU  - Ross,P
AU  - Halford,S
AU  - Peters,J
AU  - Balkissoon,J
AU  - Chaplin,DJ
AU  - Padhani,AR
AU  - Rustin,GJ
DO  - 10.1158/1078-0432.CCR-11-2414
EP  - 1425
PY  - 2012///
SN  - 1078-0432
SP  - 1415
TI  - Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors
T2  - Clin Cancer Res
UR  - http://dx.doi.org/10.1158/1078-0432.CCR-11-2414
UR  - http://www.ncbi.nlm.nih.gov/pubmed/22235096%20http://clincancerres.aacrjournals.org/content/18/5/1415.full.pdf
VL  - 18
ER  -
Download