Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

Sonnichsen, Daryl; Birkhofer, Martin; Ferreira, Irene; Noel, D

doi:10.1007/s002800050887

Cited by 14 publications

(8 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5-FU is an analogue of uracil, which is an essential component during cell division and integrates into cellular DNA, inhibiting cell division 14 . However, 5-FU in the human body is degraded by a) conversion into secondary and tertiary metabolites and b) degradation by dihydropyrimidine dehydrogenase (DPD) 14,15 . Due to these processes, the half-life of 5-FU in circulation in human body is very short (∼ 30 minutes), while DPD activity clears ∼80% of 5-FU produced 14,16 .…”

Section: Narrativementioning

confidence: 99%

“…3a,b). The dose of 100 μM for tegafur was chosen based on the concentration that is achieved by oral uptake of tegafur-uracil (UFT), C max = 31.159 μM, Area Under Curve (AUC) = 121 μM × min 15 . Furthermore, IC-50 values (Table 2, Supplementary Fig.…”

Section: Narrativementioning

confidence: 99%

“…While tegafur and uracil are actively metabolized by hepatocytes, 5-FU is actively produced and subsequently converted by hepatocytes into secondary metabolites 14 . Further, the bioavailability of 5-FU is signifcantly lower ( C max = 0.847 μM) when compared with tegafur ( C max = 31.159 μM) due to its rapid clearance 14,15 . In co-culture drug exposure experiments within two-chamber microfabricated device, measurements were made at the end of incubation (24 hours), and are shown in Supplementary Fig.…”

Section: Narrativementioning

confidence: 99%

See 2 more Smart Citations

A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity

et al. 2015

View full text Add to dashboard Cite

To evaluate drug and metabolite efficacy on a target organ, it is essential to include metabolic function of hepatocytes, and to evaluate metabolite influence on both hepatocytes and the target of interest. Herein, we have developed a two-chamber microfabricated device separated by a membrane enabling communication between hepatocytes and cancer cells. The microscale environment created enables cell co-culture in a low media-to-cell ratio leading to higher metabolite formation and rapid accumulation, which is lost in traditional plate cultures or other interconnected models due to higher culture volumes. We demonstrate the efficacy of this system by metabolism of tegafur by hepatocytes resulting in cancer cell toxicity.

show abstract

Section: Narrativementioning

confidence: 99%

Section: Narrativementioning

confidence: 99%

Section: Narrativementioning

confidence: 99%

See 1 more Smart Citation

A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The fact that patients were not their own controls limits the conclusions of the latter study but, from a practical point of view, it would be particularly important to know the magnitude of the difference in 5-FU availability between morning and afternoon administration of UFT. A study was undertaken to address the possible pharmacokinetic influence of concurrent oral administration of UFT and LV (Meropol et al, 1999). When LV was coadministered with UFT, there was no significant impact on the fates of FT, uracil and, particularly, on 5-FU AUC values.…”

Section: Dpd Inhibitionmentioning

confidence: 99%

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

2004

View full text Add to dashboard Cite

The main purpose of the present review article was to shed light on the different 5-fluorouracil (5-FU) prodrugs by underlining their respective pharmacological features in terms of metabolic activation, dihydropyrimidine dehydrogenase inhibition, pharmacokinetic profile and biomodulation ability. Oral fluoropyrimidines differ particularly as concerns their pharmacokinetic profile and especially in the delivery of circulating 5-FU. More clinical studies need to be performed incorporating tumour predictive markers during oral fluoropyrimidine-based treatment. The new possibilities are to achieve pharmacomodulation of oral fluoropyrimidines, notably for UFT and capecitabine, that open up the prospect of establishing significant novel treatment protocols based on drug combinations.

show abstract

“…Tegafur and uracil (UFT) are composed of a 1 : 4 xed molar ratio of Ftorafur (tegafur) and uracil (187). Tegafur is a uorouracil prodrug, and uracil competes with uorouracil as a substrate for dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for uorouracil catabolism.…”

Section: Newer Drugs and Drug Combinationsmentioning

confidence: 99%

A Systematic Overview of Chemotherapy Effects in Colorectal Cancer

Ragnhammar¹

2001

Acta Oncologica

View full text Add to dashboard Cite

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scienti c literature are described separately (Acta Oncol 2001; 40: 155 -65). This synthesis of the literature on adjuvant and palliative therapy with cytostatics for colorectal cancer is based on 208 scienti c articles, including eight meta-analyses and 162 randomised studies. These studies involve approximately 126 800 patients. The conclusions reached can be summarized into the following points:The bene t of postoperative adjuvant chemotherapy with uorouracil and levamisole in patients with colon cancer stage Dukes' C was demonstrated more than ten years ago in two phase III trials. There was a reduction of recurrence from 56% to 39% and reduction of death from 51% to 40% after more than ve years of follow-up. Although this combination has been widely accepted as standard adjuvant treatments for stage Dukes' C colon cancer, there is still debate on whether adjuvant treatment with uorouracil alone would be equally ef cacious. Several phase III trials with postoperative adjuvant chemotherapy with uorouracil and leucovorin in patients with colon cancer stage Dukes' C have demonstrated a similar statistically signi cant improvement in disease-free and overall survival in comparison with a control arm. Six months of treatment with uorouracil and leucovorin is as ef cient as twelve months of uorouracil and levamisole. This treatment is, thus, recommended for routine use. No convincing bene t from adjuvant chemotherapy is proven in colon cancer stage Dukes' B although some randomised trials have shown the same relative survival gain as seen in stage Dukes' C. There is less knowledge on survival bene ts from adjuvant chemotherapy for Dukes' stage B and C rectal cancer. In small randomised trials, postoperative radiochemotherapy has, however, improved survival to the same extent as chemotherapy in colon cancer Dukes' stage C. A meta-analysis of nine randomised trials revealed a small but statistically signi cant bene t in ve-year survival and a reduction in the risk of death for the patients receiving immediate postoperative portal vein infusion compared with controls. At present, however, the use of portal vein infusion or intraperitoneal therapy outside of a research trial cannot be recommended in the light of the limited effects. This conclusion is further supported by similarly limited effects in two recently reported very large European multicentre trials. In advanced colorectal cancer, chemotherapy may prolong survival, decrease tumour-related symptoms, improve general well-being or maintain it at a high level for a longer time period compared with best supportive care. These effects have been seen using systemic chemotherapy and using regional chemotherapy in patients with metastases limited to the liver. Subjective responses and quality of life improvements are seen more frequently than objective tumour remissions. Altho...

show abstract

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

Cited by 14 publications

References 7 publications

A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity

A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity

Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation

A Systematic Overview of Chemotherapy Effects in Colorectal Cancer

Contact Info

Product

Resources

About