Imperial College London
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ProfessorPatriciaPrice

Faculty of Medicine, Department of Surgery & Cancer

Visiting Professor
 
 
 
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Contact

 

p.price

 
 
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Location

 

BN1/24 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Harte:1999,
author = {Harte, RJ and Matthews, JC and O'Reilly, SM and Tilsley, DW and Osman, S and Brown, G and Luthra, SJ and Brady, F and Jones, T and Price, PM},
journal = {J Clin Oncol},
pages = {1580--1588},
title = {Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa},
url = {http://www.jco.org/cgi/reprint/17/5/1580.pdf},
volume = {17},
year = {1999}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PURPOSE: To evaluate the effect of N-phosphonacetyl-L-aspartate (PALA), folinic acid (FA), and interferon alfa (IFN-alpha) biomodulation on plasma fluorouracil (5FU) pharmacokinetics and tumor and liver radioactivity uptake and retention after [18F]-fluorouracil (5-[18F]-FU) administration. PATIENTS AND METHODS: Twenty-one paired pharmacokinetic studies were completed on patients with colorectal, gastric, and hepatocellular cancer, utilizing positron emission tomography (PET), which allowed the acquisition of tumor, normal tissue, and plasma pharmacokinetic data and tumor blood flow (TBF) measurements. The first PET study was completed when the patient was biomodulator-naive and was repeated on day 8 after the patient had been treated with either PALA, FA, or IFN-alpha in recognized schedules. RESULTS: TBF was an important determinant of tumor radioactivity uptake (r = .90; P < .001) and retention (r = .96; P < .001), for which radioactivity represents a composite signal of 5-[18F]-FU and [18F]-labeled metabolites and catabolites. After treatment with PALA, TBF decreased (four of four patients; P = .043), as did tumor radioactivity exposure (five of five patients; P = .0437), with no change in plasma 5FU clearance. With FA treatment, there were no differences observed in whole-body metabolism, plasma 5FU clearance, or tumor and liver pharmacokinetics. IFN-alpha had measurable effects on TBF and 5-[18F]-FU metabolism but had no apparent affect on liver blood flow. CONCLUSION: The administration of PALA and IFN-alpha produced measurable changes in plasma, tumor, and liver pharmacokinetics after 5-[18F]-FU administration. No changes were observed after FA administration. In vivo effects may negate the anticipated therapeutic advantage of 5FU biomodulation with some agents.
AU  - Harte,RJ
AU  - Matthews,JC
AU  - O'Reilly,SM
AU  - Tilsley,DW
AU  - Osman,S
AU  - Brown,G
AU  - Luthra,SJ
AU  - Brady,F
AU  - Jones,T
AU  - Price,PM
EP  - 1588
PY  - 1999///
SP  - 1580
TI  - Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa
T2  - J Clin Oncol
UR  - http://www.jco.org/cgi/reprint/17/5/1580.pdf
VL  - 17
ER  -
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