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Uptake of 5-fluorouracil (5-FU) in peritoneal metastases in relation to the route of drug administration and tumour debulking surgery: an autoradiographic study in the rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Biochemistry.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science.
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2004 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 40, no 1, 142-147 p.Article in journal (Refereed) Published
Abstract [en]

Patients with peritoneal metastases from colorectal cancer have a poor prognosis. Aggressive treatment by debulking surgery and intraperitoneal (i.p.) chemotherapy has been suggested as an alternative therapy. However, the drug penetrance into the tumour in relation to the administration route and surgical reduction of the tumour is not well known. We compared locoregional administration with intravenous (i.v.) injection. Thirty-four in-bred rats with peritoneal metastases were randomly allocated into eight groups and injected with 14C-labelled 5-fluorouracil (5-FU) either through the i.v. or i.p. route, with or without a preceding tumour debulking, and were sacrificed after 2 or 8 h. Tumour radioactivity was visualised by autoradiography and quantified by a computer-based image analysis. After 8 h, 19 debulked and i.p.-injected tumours had a higher drug uptake, 63.2+/-28 (mean+/-standard deviation (SD)) kBq/g than 62 native i.p.-injected tumours (32.8+/-14) or 22 debulked and i.v.-injected tumours (18.5+/-18, P=0.002). After 8 h, 9 small tumours (<median 571 pixels) which underwent i.p. injection and tumour reduction had a higher drug uptake (77.4+/-26) than 29 non-debulked and i.p.-injected (35.1+/-17) or eight debulked and i.v. injected tumours (23.0+/-16, P=0.004). For larger tumours (>/=median 571 pixels), 16 debulked and i.p.-injected tumours had a higher radioactivity (drug uptake) (150.7+/-63) at 2 h than 49 i.p.-injected native tumours (48.5+/-59) or 11 reduced and i.v.-injected tumours (19.9+/-13, P=0.03). At 8 h, 10 debulked and i.p.-injected tumours had a higher drug uptake (50.3+/-24) than 33 native and i.p.-injected (30.8+/-10) or 14 debulked and i.v.-injected tumours (16.0+/-19, P=0.001). These results indicate that a debulking procedure and locoregional treatment of peritoneal metastases is associated with an increased level of 5-FU in the tumours.

Place, publisher, year, edition, pages
2004. Vol. 40, no 1, 142-147 p.
Keyword [en]
Adenocarcinoma, Animals, Antimetabolites; Antineoplastic/administration & dosage/*pharmacokinetics, Autoradiography, Colonic Neoplasms, Female, Fluorouracil/administration & dosage/*pharmacokinetics, Injections; Intraperitoneal, Injections; Intravenous, Peritoneal Neoplasms/drug therapy/*metabolism/*secondary, Random Allocation, Rats, Rats; Wistar, Research Support; Non-U.S. Gov't
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-74843DOI: 10.1016/S0959-8049(03)00667-1PubMedID: 14687798OAI: oai:DiVA.org:uu-74843DiVA: diva2:102753
Available from: 2005-11-30 Created: 2005-11-30 Last updated: 2017-12-14Bibliographically approved

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Mahteme, HaileSundin, AndersGraf, Wilhelm

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Department of Surgical SciencesToxicologyDepartment of Radiology, Oncology and Radiation SciencePharmaceutical BiochemistryDepartment of Information Science
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