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Uptake of 5-fluorou...
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
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- Mahteme, Haile (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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- Larsson, B (author)
- Uppsala universitet,Avdelningen för toxikologi
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- Sundin, Anders (author)
- Uppsala universitet,Institutionen för radiologi, onkologi och strålningsvetenskap,Avdelningen för farmaceutisk biokemi
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- Khamis, Harry (author)
- Uppsala universitet,Institutionen för informationsvetenskap
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- Graf, Wilhelm (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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(creator_code:org_t)
- 2004
- 2004
- English.
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In: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 40:1, s. 142-147
- Related links:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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), 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.
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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