Carbogen and Nicotinamide Increase Blood Flow and 5-Fluorouracil Delivery but not 5-Fluorouracil Retention in Colorectal Cancer Metastases in Patients

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Bibliographische Detailangaben
Zeitschriftentitel:	Clinical Cancer Research
Personen und Körperschaften:	Gupta, Nishi, Saleem, Azeem, Kötz, Barbara, Osman, Safiye, Aboagye, Eric O., Phillips, Robert, Vernon, Clare, Wasan, Harpreet, Jones, Terry, Hoskin, Peter J., Price, Patricia M.
In:	Clinical Cancer Research, 12, 2006, 10, S. 3115-3123
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	American Association for Cancer Research (AACR)
Schlagwörter:	Cancer Research Oncology

Details
Zusammenfassung:	<jats:title>Abstract</jats:title> <jats:p>Purpose: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases.</jats:p> <jats:p>Experimental Design: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered.</jats:p> <jats:p>Results: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mLblood/min/mLtissue) increased in metastases (mean change = 52%, range −32% to +261%, P = 0.024), but decreased in kidney (mean change = −42%, range −82% to −11%, P = 0.0005) and liver (mean change = −34%, range −43% to −26%, P = 0.031). 5-FU uptake at 3.75 minutes (m2/mL) increased in tumor (mean change = 40%, range −39% to +196%, P = 0.06) and decreased in kidney (mean change = −25%, range −71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range −23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention.</jats:p> <jats:p>Conclusion: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.</jats:p>
Umfang:	3115-3123
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.ccr-05-0513