5--deoxy-5-fluorocytidine and doxifluridine

Capecitabine (Cape) is a prodrug that is metabolized into 5'-deoxy-5-fluorocytidine (DFCR), 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5-FU) after oral administration. A liquid chromatography-tandem mass spectrometry method for the simultaneous determination of capecitabine and its three metabolites in human plasma was developed and validated. The ex vivo conversion of DFCR to DFUR in human blood was investigated and an appropriate blood sample handling condition was recommended. Capecitabine and its metabolites were extracted from 100 μL of plasma by protein precipitation. Adequate chromatographic retention and efficient separation were achieved on an Atlantis dC18 column under gradient elution. Interferences from endogenous matrix and the naturally occurring heavy isotopic species were avoided. Detection was performed in electrospray ionization mode using a polarity-switching strategy. The method was linear in the range of 10.0-5000 ng/mL for Cape, DFCR, and DFUR, and 2.00-200 ng/mL for 5-FU. The LLOQ was established at 10.0 ng/mL for Cape, DFCR, and DFUR, and 2.00 ng/mL for 5-FU. The inter- and intra-day precisions were less than 13.5%, 11.1%, 9.7%, and 11.4%, and the accuracy was in the range of -13.2% to 1.6%, -2.4% to 2.5%, -7.1% to 8.2%, and -2.0% to 3.8% for Cape, DFCR, DFUR, and 5-FU, respectively. The matrix effect was negligible under the current conditions. The mean extraction recoveries were within 105-115%, 92.6-101%, 94.0-100%, and 85.1-99.9% for Cape, DFCR, DFUR, and 5-FU, respectively. Stability testing showed that the four analytes remained stable under all relevant analytical conditions. This method has been applied to a clinical bioequivalence study.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Chromatography, High Pressure Liquid; Deoxycytidine; Floxuridine; Fluorouracil; Humans; Male; Neoplasms; Tandem Mass Spectrometry; Therapeutic Equivalency

To describe concentration versus time profiles of capecitabine and its metabolites 5'-DFUR, 5'-DFCR and 5-FU, depending on tablet formulation and on frequent and/or relevant genetic polymorphisms of cytidine deaminase, dihydropyrimidine dehydrogenase, thymidylate synthase and methylenetetrahydrofolate reductase (MTHFR).. In 46 cancer patients on chronic capecitabine treatment, who voluntarily participated in the study, individual therapeutic doses were replaced on four consecutive mornings by the study medication. The appropriate number of 500 mg test (T) or reference (R) capecitabine tablets was given in randomly allocated sequences TRTR or RTRT (replicate design). Average bioavailability was assessed by ANOVA.. Thirty female and 16 male patients suffering from gastrointestinal or breast cancer (mean age 53.4 years; mean dose 1739 mg) were included. The T/R ratios for AUC0-t(last) and C max were 96.7 % (98 % CI 90.7-103.2 %) and 87.2 % (98 % CI 74.9-101.5 %), respectively. Within-subject variability for AUC0-t(last) and C max (coefficient of variation for R) was 16.5 and 30.2 %, respectively. Similar results were seen for all metabolites. No serious adverse events occurred. For the MTHFR C677T (rs1801133) genotype, an increasing number of 677C alleles showed borderline correlation with an increasing elimination half-life of capecitabine (p = 0.043).. The extent of absorption was similar for T and R, but the rate of absorption was slightly lower for T. While such differences are not considered as clinically relevant, formal bioequivalence criteria were missed. A possible, probably indirect role of the MTHFR genotype in pharmacokinetics of capecitabine and/or 5-FU should be investigated in further studies.

Topics: Activation, Metabolic; Administration, Oral; Adult; Aged; Alleles; Antimetabolites, Antineoplastic; Area Under Curve; Capecitabine; Carboxylesterase; Cytidine Deaminase; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Female; Floxuridine; Fluorouracil; Genotype; Humans; Liver; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prodrugs; Tablets; Therapeutic Equivalency; Thymidine Phosphorylase; Thymidylate Synthase

The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ≥70 years and <60 years were compared in SWOG0030.. Twenty-nine unresectable colorectal cancer patients were stratified to either ≥70 or <60 years of age, where the disposition of capecitabine and its metabolites were compared.. Notable increase in capecitabine area under the curve (AUC) was accompanied by reduction in capecitabine clearance in ≥70 years patients (P<0.05). No difference in 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5FU) AUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in females.. Increases in capecitabine Cmax and AUC was observed in patients ≥70 years when compared with younger patients who were >60 years.

Topics: Age Factors; Aged; Antimetabolites, Antineoplastic; Area Under Curve; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Floxuridine; Fluorouracil; Glomerular Filtration Rate; Humans; Male; Metabolic Clearance Rate; Middle Aged; Sex Factors

In view of a potential gain in anticancer activity in advanced colorectal cancer (ACRC), there has been considerable interest in using a higher than the approved standard dose of capecitabine (CCB) combined with oxaliplatin. This pharmacokinetic study was designed to evaluate whether CCB is metabolized at the same extent when administered as a monotherapy in two different dose regimens, comparing standard dose (CCB 1) and intensified dose (CCB 2).. Seven patients suffering from ACRC received subsequently two CCB schedules: In the standard schedule, 1,250 mg/m² CCB p.o. twice daily for 2 weeks was administered, after a pause of 1 week, a dose-intensified CCB 2 schedule was given: 1,750 mg/m² CCB p.o. twice daily for 1 week to be followed by 1 week rest. Due to this paired cross over design a direct comparison for each single patient was feasible.. In both schedules, mean peak plasma concentrations of CCB occurred at about 50 min, those of metabolites shortly later (range 54-80 min). Peak plasma concentrations were about 10% (CCB, DFCR) and 40% (DFUR) higher in the CCB 2 regimen. According to the higher dose of CCB in the dose-intensified regimen (+40%), the AUC(last) values increased by 34% (CCB), 20% (DFCR) and 58% (DFUR), respectively.. The results indicate that higher doses of CCB are metabolized approximately dose-dependent compared to the standard dose. No indices for a saturation of metabolizing processes or any significant delay of elimination rate was observed. The immediate 5FU precursor DFUR was formed at a 50% higher extent (expressed as AUC(last) values) than in the standard CCB 1 schedule. From the pharmacokinetic point of view, this increased formation rate suggests clinical importance in regard to metabolic activation of CCB.

Topics: Aged; Antimetabolites, Antineoplastic; Area Under Curve; Capecitabine; Colorectal Neoplasms; Cross-Over Studies; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Floxuridine; Fluorouracil; Humans; Male; Middle Aged

Capecitabine is an anticancer agent and is the oral prodrug of 5-fluorouracil (5-FU). In this study, an ultra-high performance liquid chromatography coupled to turbo ion spray tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to quantify capecitabine and its metabolites including 5'-deoxy-5-fluorocytidine (5'-dFCR), 5'-deoxy-5-fluorouridine (5'-dFUR), 5-FU, and fluoro-β-alanine (FBAL) in lithium heparinized human plasma. Analytes were extracted by protein precipitation, chromatographically separated by Acquity UPLC HSS T3 column with gradient elution, and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. Capecitabine and 5'-dFCR were quantified in positive ion mode and 5'-dFUR, 5-FU, and FBAL were quantified in negative ion mode. The total chromatographic run time was 9 min. Stable isotopically labeled internal standards were used for all analytes. The assay was validated over the range from 25.0 to 2,500 ng/mL for capecitabine, 10.0 to 1,000 ng/mL for 5'-dFCR, 5'-dFUR, and 5-FU and 50 to 5,000 ng/ mL for FBAL in human plasma. Validation results have shown the developed assay allows for reliable quantitative analysis of capecitabine, 5'-dFCR, 5'-dFUR, 5-FU, and FBAL in plasma samples. Capecitabine is an anticancer agent and is the oral prodrug of 5-fluorouracil (5-FU). In this study, an ultra-high performance liquid chromatography coupled to turbo ion spray tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to quantify capecitabine and its metabolites including 5'-deoxy-5-fluorocytidine (5'-dFCR), 5'-deoxy-5-fluorouridine (5'-dFUR), 5-FU, and fluoro-β-alanine (FBAL) in lithium heparinized human plasma. Analytes were extracted by protein precipitation, chromatographically separated by Acquity UPLC HSS T3 column with gradient elution, and analyzed with a tandem mass spectrometer equipped with an electrospray ionization source. Capecitabine and 5'-dFCR were quantified in positive ion mode and 5'-dFUR, 5-FU, and FBAL were quantified in negative ion mode. The total chromatographic run time was 9 min. Stable isotopically labeled internal standards were used for all analytes. The assay was validated over the range from 25.0 to 2,500 ng/mL for capecitabine, 10.0 to 1,000 ng/mL for 5'-dFCR, 5'-dFUR, and 5-FU and 50 to 5,000 ng/ mL for FBAL in human plasma. Validation results have shown the developed assay allows for reliable quantitative analysis of capecitabine, 5'-dFCR, 5'-dFUR,

Topics: beta-Alanine; Capecitabine; Chromatography, High Pressure Liquid; Chromatography, Liquid; Fluorouracil; Humans; Lithium; Prodrugs; Tandem Mass Spectrometry

Capecitabine is an oral prodrug of the anticancer drug 5-fluorouracil (5-FU). The primary aim of this study was to develop a pharmacokinetic model for capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine (dFCR), 5'-deoxy-5-fluorouridine (dFUR), 5-FU, and fluoro-β-alanine (FBAL) using data from a heterogeneous population of cancer patients (n = 237) who participated in seven clinical studies. A four-transit model adequately described capecitabine absorption. Capecitabine, dFCR, and FBAL pharmacokinetics were well described by two-compartment models, and dFUR and 5-FU were subject to flip-flop pharmacokinetics. Partial and total gastrectomy were associated with a significantly faster capecitabine absorption resulting in higher capecitabine and metabolite peak concentrations. Patients who were heterozygous polymorphic for a genetic mutation encoding dihydropyrimidine dehydrogenase, the DPYD*2A mutation, demonstrated a 21.5% (relative standard error 11.2%) reduction in 5-FU elimination. This comprehensive population model gives an extensive overview of capecitabine and metabolite pharmacokinetics in a large and heterogeneous population of cancer patients.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Capecitabine; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Female; Floxuridine; Gastrectomy; Humans; Male; Middle Aged; Neoplasms; Pharmacogenomic Variants; Prodrugs

Several retrospective studies have shown that the antitumor efficacy of capecitabine-containing chemotherapy decreases when co-administered with a proton pump inhibitor (PPI). Although a reduction in capecitabine absorption by PPIs was proposed as the underlying mechanism, the effects of PPIs on capecitabine pharmacokinetics remain unclear. We prospectively examined the effects of rabeprazole on the pharmacokinetics of capecitabine and its metabolites.. We enrolled patients administered adjuvant capecitabine plus oxaliplatin (CapeOX) for postoperative colorectal cancer (CRC) patients and metastatic CRC patients receiving CapeOX with/without bevacizumab. Patients receiving a PPI before registration were allocated to the rabeprazole group, and the PPI was changed to rabeprazole (20 mg/day) at least 1 week before the initiation of capecitabine treatment. On day 1, oral capecitabine (1000 mg/m. Five and 9 patients enrolled between September 2017 and July 2018 were allocated to rabeprazole and control groups, respectively. No significant effects of rabeprazole on area under the plasma concentration-time curve divided by capecitabine dose for capecitabine and its three metabolites were observed. Rabeprazole did not affect the proliferation inhibition of colon cancer cells by the respective capecitabine metabolites.. Rabeprazole does not affect capecitabine pharmacokinetics.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Capecitabine; Cell Proliferation; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Deoxycytidine; Drug Interactions; Female; Floxuridine; Fluorouracil; Humans; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Rabeprazole

Topics: Animals; Antimetabolites, Antineoplastic; Capecitabine; Circadian Rhythm; Deoxycytidine; Floxuridine; Fluorouracil; Male; Prodrugs; Rats, Wistar

Drug monitoring is a useful tool for obtaining detailed information about the disposition of a drug in an individual patient during chemotherapy. According to the international guidelines, the analytical assay for quantification of a compound in biological samples must be validated. Among a number of parameters, peak purity is an important requirement.. We analyzed pharmacokinetics in patients who received chemotherapy with capecitabine and up to 10 various co-medications.. Out of seven investigated co-administered drugs, we found evidence that the proton pump inhibitor pantoprazole causes peak interferences with capecitabine during high-performance liquid chromatography analysis. Therefore quantification of capecitabine in plasma samples can be inaccurate.. We recommend an altered time schedule for co-administered drugs or changing the mobile phase used in the assay.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Deoxycytidine; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Floxuridine; Fluorouracil; Humans; Pantoprazole; Proton Pump Inhibitors

Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.. Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study. In the first cycle CCB was given alone at doses of 1,250 mg/m2 bi-daily for two weeks with one week rest. In the second cycle BVZ co-administration started simultaneously with oral intake of CCB by short infusion of 7.5 mg/kg.. Mean plasma concentration time curves of CCB and its metabolites were insignificantly lower in the BVZ combination regimen compared to CCB monotherapy. After repeated cycles of BVZ no significant pharmacokinetic interaction was observed.. From the pharmacokinetic point of view and in agreement with numerous clinical study data, co-administration of BVZ with CCB appears to be safe and efficient.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Floxuridine; Fluorouracil; Humans; Male; Middle Aged

A simple and precise analytical method for the determination of 5'deoxy-5-fluorocytidine (DFCR) and 5'deoxy-5-fluorouridine (DFUR), the enzymatically formed metabolites of capecitabine in plasma, was developed using a reversed-phase high performance liquid chromatography gradient method with external standard method. Blood samples were analyzed after separation of DFCR/DFUR by solid-phase extraction from matrix compounds using a C16 amide reversed-phase column operated at a flow rate of 0.8 ml/min in gradient elution mode with a mobile phase composed of water-methanol (10 mM ammonium acetate in water; m/v). Excellent recoveries in plasma ranging from 77.5-99.12% for DFCR and 84.70-99.15% for DFUR, respectively, were obtained. For both compounds the calibration curves were linear over the range from 0.156 to 5.0 μg/ml. The present assay is robust, selective and sensitive, and is being applied in our laboratories to monitor plasma concentrations of DFCR and DFUR in clinical phase I and phase II studies.

Topics: Calibration; Chromatography, High Pressure Liquid; Deoxycytidine; Drug Monitoring; Drug Stability; Floxuridine; Humans; Limit of Detection; Outpatients; Sensitivity and Specificity; Solid Phase Extraction

A rapid and selective liquid chromatography/tandem mass spectrometric method was developed for the simultaneous determination of capecitabine and its metabolites 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouracil (5'-DFUR), 5-fluorouracil (5-FU) and dihydro-5-fluorouracil (FUH(2)) in human plasma. A 200 microL human plasma aliquot was spiked with a mixture of internal standards fludarabine and 5-chlorouracil. A single-step protein precipitation method was employed using 10% (v/v) trichloroacetic acid in water to separate analytes from bio-matrices. Volumes of 20 microL of the supernatant were directly injected onto the HPLC system. Separation was achieved on a 30 x 2.1 mm Hypercarb (porous graphitic carbon) column using a gradient by mixing 10 mm ammonium acetate and acetonitrile-2-propanol-tetrahydrofuran (1 : 3 : 2.25, v/v/v). The detection was performed using a Finnigan TSQ Quantum Ultra equipped with the electrospray ion source operated in positive and negative mode. The assay quantifies a range from 10 to 1000 ng/mL for capecitabine, from 10 to 5000 ng/mL for 5'-DFCR and 5'-DFUR, and from 50 to 5000 ng/mL for 5-FU and FUH(2) using a plasma sample of 200 microL. Correlation coefficients (r(2)) of the calibration curves in human plasma were better than 0.99 for all compounds. At all concentration levels, deviations of measured concentrations from nominal concentration were between -4.41 and 3.65% with CV values less than 12.0% for capecitabine, between -7.00 and 6.59% with CV values less than 13.0 for 5'-DFUR, between -3.25 and 4.11% with CV values less than 9.34% for 5'-DFCR, between -5.54 and 5.91% with CV values less than 9.69% for 5-FU and between -4.26 and 6.86% with CV values less than 14.9% for FUH(2). The described method was successfully applied for the evaluation of the pharmacokinetic profile of capecitabine and its metabolites in plasma of treated cancer patients.

Topics: 1-Propanol; Acetonitriles; Antimetabolites, Antineoplastic; Capecitabine; Chemical Precipitation; Chromatography, High Pressure Liquid; Deoxycytidine; Drug Stability; Floxuridine; Fluorouracil; Furans; Humans; Linear Models; Pyrimidines; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Trichloroacetic Acid; Uracil; Vidarabine

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Floxuridine; Fluorouracil; Humans; Organoplatinum Compounds; Oxaliplatin

A rapid high-performance liquid chromatography method has been developed for simultaneous determination of capecitabine and its metabolites: 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU). 5'-DFCR was synthesized by hydrolyzing capecitabine using commercially available carboxyl esterase (CES) and characterized by NMR, mass spectrometry and elemental analysis. Base-line separations between capecitabine, 5'-DFCR, 5'-DFUR and 5-FU were found with symmetrical peak shapes on a Discovery RP-amide C16 column using 10 mM ammonium acetate at pH 4.0 and methanol as the mobile phase. The retention times of capecitabine, 5'-DFCR, 5'-DFUR and 5-FU were 8.9, 5.0, 5.3 and 3.0 min, respectively. Linear calibration curves were obtained for each compound across a range from 1 to 500 microg ml(-1). The intra- and inter-day relative standard deviations (%RSD) were <5%. A single-step protein precipitation method was employed for separation of the analytes from bio-matrices. Greater than 85% recoveries were obtained for capecitabine, 5'-DFCR, 5'-DFUR and 5-FU from bio-fluids including mouse plasma, mouse serum and rabbit bile.

Topics: Animals; Bile; Calibration; Capecitabine; Chromatography, High Pressure Liquid; Deoxycytidine; Floxuridine; Fluorouracil; Mice; Plasma; Rabbits; Reproducibility of Results; Serum

A reverse-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of capecitabine, its intermediate metabolites (DFCR, DFUR) and the active metabolite 5-fluorouracil in mouse plasma, liver and human xenograft tumours. The method was also cross-validated in human plasma and human tumour for clinical application. The method has greater sensitivity than previously published methods with an equivalent accuracy and precision. It uses less biological material (plasma, tissue) and should therefore be applicable to biopsies in patients treated with capecitabine.

Topics: Animals; Capecitabine; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Deoxycytidine; Drug Stability; Floxuridine; Fluorouracil; Humans; Liver; Mice; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization

Capecitabine, an anticancer prodrug, is thought to be biotransformed into active 5-fluorouracil (5-FU) by three enzymes. After oral administration, capecitabine is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase (CES), then 5'-DFCR is converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase. 5'-DFUR is activated to 5-FU by thymidine phosphorylase. Although high activities of drug metabolizing enzymes are expressed in human liver, the involvement of the liver in capecitabine metabolism is not fully understood. In this study, the metabolism of capecitabine in human liver was investigated in vitro. 5'-DFCR, 5'-DFUR, and 5-FU formation from capecitabine were investigated in human liver S9, microsomes, and cytosol in the presence of the inhibitor of dihydropyrimidine dehydrogenase, 5-chloro-2,4-dihydroxypyridine. 5'-DFCR, 5'-DFUR, and 5-FU were formed from capecitabine in cytosol and in the combination of microsomes and cytosol. Only 5'-DFCR formation was detected in microsomes. The apparent K(m) and V(max) values of 5-FU formation catalyzed by cytosol alone and in combination with microsomes were 8.1 mM and 106.5 pmol/min/mg protein, and 4.0 mM and 64.0 pmol/min/mg protein, respectively. The interindividual variability in 5'-DFCR formation in microsomes and cytosol among 14 human liver samples was 8.3- and 12.3-fold, respectively. Capecitabine seems to be metabolized to 5-FU in human liver. 5'-DFCR formation was exhibited in cytosol with large interindividual variability, although CES is located in microsomes in human liver. In the present study, it has been clarified that the cytosolic enzyme would be important in 5'-DFCR formation, as is CES.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Cytosol; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Floxuridine; Fluorouracil; Humans; In Vitro Techniques; Microsomes, Liver; Prodrugs; Pyridines; Thymidine Phosphorylase

In metastatic colorectal cancer the oral 5-fluorouracil (5FU) prodrug capecitabine is used with increasing frequency as an alternative to i.v. 5FU administration. The rate of conversion of capecitabine into 5'deoxy-5-fluorouridine has been related to tumor response, and 5FU catabolites have been associated with 5FU-related systemic toxicity. Here we demonstrate for the first time that capecitabine, its metabolites 5'deoxy-5-fluorocytidine and 5'deoxy-5-fluorouridine, and its catabolites 5-fluoro-ureido-propionic acid, alpha-fluoro-beta-alanine, and alpha-fluoro-beta-alanine-bile acid conjugate can be monitored in vivo by (19)fluorine magnetic resonance spectroscopy ((19)F MRS) in the liver of patients with metastatic colorectal cancer. Moreover, we demonstrate an improved signal-to-noise ratio and spectral resolution of the (19)F MRS spectra when measurements are performed at 3 T field strength as compared with measurements at the common clinical field strength of 1.5 T. We conclude that assessment of capecitabine metabolism in patients by (19)F MRS is a promising noninvasive tool for the prediction of its efficacy and toxicity, especially at the now currently available clinical field strength of 3 T.

Topics: Aged; Antimetabolites, Antineoplastic; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Female; Floxuridine; Fluorine; Fluorouracil; Humans; Liver; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged; Prodrugs

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Breast Neoplasms; Capecitabine; Deoxycytidine; Electrophoresis, Capillary; Extracellular Space; Floxuridine; Fluorouracil; Humans; Prodrugs; Skin Neoplasms; Tissue Distribution