Abstract | PURPOSE: METHODS: Eighty patients scheduled for colorectal resection with indication of colorectal cancer were randomised into four groups to receive leucovorin at 0, 60, 200, or 500 mg/m(2), respectively. Blood samples were taken 10 and 30 min after leucovorin administration. Biopsy samples from tumour and mucosa were collected and snap-frozen at surgery. The levels of THF, methyleneTHF, and methylTHF in tumour and mucosa were assessed by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-MS/MS) and the results were related to clinical diagnosis and therapeutic regimens. RESULTS: The folate levels in tissue revealed extensive inter-individual variability. The mean methyleneTHF value for the four treatment groups were 880, 1,769, 3,024 and 3,723 pmol/gww. Only half of the patients who received 60 mg/m(2) leucovorin had higher levels of methyleneTHF in tumour than patients who received 0 mg/m(2) leucovorin. Rectal cancer patients had significantly lower levels of methyleneTHF compared with colon cancer patients. CONCLUSIONS: There was a large inter-patient variability of tissue folate levels in colorectal cancer patients after supplementation with leucovorin at standardised dosage. High leucovorin doses were needed to exceed baseline methyleneTHF values, especially in rectal cancer patients. The results indicate that the standardised leucovorin dose may be insufficient to attain the full antitumour effect of 5-FU. Further studies are needed to establish whether higher dosage yields a better treatment response.
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Authors | Helena Taflin, Yvonne Wettergren, Elisabeth Odin, Kristoffer Derwinger |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 74
Issue 6
Pg. 1167-74
(Dec 2014)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 25238909
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Tetrahydrofolates
- 5,10-methylenetetrahydrofolic acid
- Vitamin B Complex
- 5,6,7,8-tetrahydrofolic acid
- Leucovorin
- 5-methyltetrahydrofolate
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Chromatography, Liquid
(methods)
- Colorectal Neoplasms
(drug therapy, surgery)
- Dose-Response Relationship, Drug
- Female
- Humans
- Leucovorin
(administration & dosage, therapeutic use)
- Male
- Middle Aged
- Spectrometry, Mass, Electrospray Ionization
(methods)
- Tandem Mass Spectrometry
(methods)
- Tetrahydrofolates
(analysis)
- Vitamin B Complex
(administration & dosage, therapeutic use)
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