levoleucovorin and carbogen

5-Fluorouracil remains widely used in colorectal cancer treatment more than 40 years after its development. 19F magnetic resonance spectroscopy can be used in vivo to measure 5FU's half-life and metabolism to cytotoxic fluoronucleotides. Previous studies have shown better survival associated with longer 5FU tumour half-life. This work investigated 5FU pharmacokinetics in liver metastases of colorectal cancer.. A total of 32 subjects with colorectal cancer undergoing 5FU treatment, 15 of whom had liver metastases, were examined in a 1.5T MRI scanner, using a large coil positioned over the liver. Non-localised spectra were acquired in 1-min blocks for 32 min after injection of a 5FU bolus. The 5FU half-life was measured in each subject, and averaged spectra were examined for the presence of fluoronucleotides. Associations with progression-free survival were assessed.. No association was observed between 5FU half-life, tumour burden and survival. Half-lives were all shorter than those associated with improved survival in the literature. Remarkably, in the group with liver metastases, high levels of fluoronucleotides were associated with poorer survival; this counterintuitive result may be due to the higher levels of fluoronucleotides (whose level is higher in tumour tissue than in normal liver) in patients with higher tumour burdens.. It is recommended that future studies use chemical shift imaging at higher field strengths to better resolve tumour from normal liver. Non-localised spectroscopy retains prognostic potential by enabling straightforward detection of fluoronucleotides, which are present at very low concentrations distributed throughout the tissue.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carbon Dioxide; Colon; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Oxygen; Rectum; Tumor Burden

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen-breathing enhances tumour uptake and the efficacy of 5-FU, and the method is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.

Topics: Adenocarcinoma; Animals; Antimetabolites, Antineoplastic; Biological Availability; Bone Marrow; Carbon Dioxide; Carcinoma, Transitional Cell; Colonic Neoplasms; Colorectal Neoplasms; Combined Modality Therapy; Fatal Outcome; Female; Fluorine Radioisotopes; Fluorodeoxyuridylate; Fluorouracil; Humans; Intestine, Small; Leucovorin; Liver; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neoplasms, Multiple Primary; Oxygen; Rats; Rats, Inbred WF; Sigmoid Neoplasms; Tomography, X-Ray Computed; Ultrasonography; Urinary Bladder Neoplasms