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, HaileUppsala universitet,Institutionen för kirurgiska vetenskaper (author)

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

Article/chapterEnglish2004

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2004
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LIBRIS-ID:oai:DiVA.org:uu-74843
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-74843URI
https://doi.org/10.1016/S0959-8049(03)00667-1DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

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

Added entries (persons, corporate bodies, meetings, titles ...)

Larsson, BUppsala universitet,Avdelningen för toxikologi (author)
Sundin, AndersUppsala universitet,Institutionen för radiologi, onkologi och strålningsvetenskap,Avdelningen för farmaceutisk biokemi(Swepub:uu)anderssu (author)
Khamis, HarryUppsala universitet,Institutionen för informationsvetenskap (author)
Graf, WilhelmUppsala universitet,Institutionen för kirurgiska vetenskaper(Swepub:uu)wilhgraf (author)
Uppsala universitetInstitutionen för kirurgiska vetenskaper (creator_code:org_t)

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In:European Journal of Cancer40:1, s. 142-1470959-80491879-0852

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By the author/editor: Mahteme, Haile; Larsson, B; Sundin, Anders; Khamis, Harry; Graf, Wilhelm

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