Disease relevance of Flutron

• Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer [1].
• Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery [2].
• 5'-Deoxy-5-fluorouridine selective toxicity for human tumor cells compared to human bone marrow [3].
• Pharmacology of 5'-deoxy-5-fluorouridine in patients with resistant ovarian cancer [4].
• Phase II study of doxifluridine in advanced colorectal adenocarcinoma [1].

High impact information on Flutron

• Effect of drug administration route on the therapeutic efficacy of the 5-fluorouracil (FUra) analogue doxifluridine [(5'-dFUrd); 5'-deoxy-5-fluorouridine] was investigated in Fischer CDF rats bearing a chemically induced transplantable colon carcinoma sensitive to fluoropyrimidines [5].
• The sensitivity of the transfected cells to Doxifluridine (5'-deoxy-5-fluorouridine) was higher than that of untransfected KB cells [6].
• Anticachectic activity of 5'-deoxy-5-fluorouridine in a murine tumor cachexia model, colon 26 adenocarcinoma [7].
• Among them, 5'-deoxy-5-fluorouridine could reverse a progressive weight loss and improve hypoglycemia, hyperglucocorticism, and hepatic malfunctions, as well as inhibiting the tumor growth [7].
• The pharmacokinetics of the new fluoropyrimidine 5'-deoxy-5-fluorouridine (5'-dFUrd) was investigated in twelve patients [4].

Chemical compound and disease context of Flutron

• Schedule dependency of antitumor activity in combination therapy with capecitabine/5'-deoxy-5-fluorouridine and docetaxel in breast cancer models [8].
• A prospective randomized trial comparing intravenous 5-fluorouracil and oral doxifluridine as postoperative adjuvant treatment for advanced rectal cancer [9].
• Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients [10].
• Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer [11].
• Phase II study of an oral combination of doxifluridine, prednimustine and idarubicin (FUPRIDA) for first line treatment of advanced breast cancer [12].

Biological context of Flutron

• Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans [13].
• The absolute bioavailability of 5'-deoxy-5-fluorouridine was estimated as 42% in patients with normal hepatic function and 62% in patients with impaired hepatic function [14].
• EXPERIMENTAL DESIGN: Cells were exposed to the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa(2)) and 5'-deoxy-5-fluorouridine (5'-DFUR), alone and in combination, for up to 96 h, and modifications in cell cycle, enzyme activity, and gene expression were examined [15].
• No effect was seen with the 3 colorectal cell lines on the IC50 values of three drugs not related to the MDR phenotype, 5-fluorouracil, 5'-deoxy-5-fluorouridine and cis-diaminodichloroplatinum (II) [16].
• Because the relative contribution of each of the two enzymes to these reactions is still largely unknown, we investigated the substrate specificity of TP and UP in colon cancer cells for the (fluoro)pyrimidine nucleosides thymidine (TdR), uridine (Urd), 5'-deoxy-5-fluorouridine (5'DFUR), and 5FU [17].

Anatomical context of Flutron

• The effect of Furtulon at the highest dose (1000 micromol/L) or at a lower dose (100 micromol/L) in the presence of ovarian cancer cyst fluid was not reversible after culture day 11 [18].
• Activation and cytotoxicity of 5'-deoxy-5-fluorouridine in c-H-ras transformed NIH 3T3 cells [19].
• Differential selectivity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in cultured human B lymphocytes and mouse L1210 leukemia [20].
• We identified two proto-oncogenes, nuclear receptor of T-cells (NOT) and c-fos, that were up-regulated in doxifluridine- and irinotecan-related regimens but unchanged in the 5-FU-related regimen [21].
• Determination of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of doxifluridine, in body fluids by high performance liquid chromatography [22].

Associations of Flutron with other chemical compounds

• Antiproliferative action of a novel fluorinated uridine analog, 5'-deoxy-5-fluorouridine, measured in vitro and in vivo on four different murine tumor lines [23].
• Thymidine phosphorylase (dThdPase) is an essential enzyme for the activation of the cytostatics capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) and its intermediate metabolite 5'-deoxy-5-fluorouridine (5'-dFUrd) to 5-fluorouracil (5-FUra) in tumors [24].
• Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo [25].
• CONCLUSIONS: Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy [9].
• The bioavailability of oral idarubicin and of oral doxifluridine allows for their use in an oral 3 drug regimen [12].

Gene context of Flutron

• Stimulatory effects of EGF and TGF-alpha on invasive activity and 5'-deoxy-5-fluorouridine sensitivity in uterine cervical-carcinoma SKG-IIIb cells [26].
• TS and DPD mRNA levels, which correlated to the corresponding enzyme activities, were quantified in tumor tissues before and after treatment in 40 advanced colorectal cancer patients who had been treated with Doxifluridine (5'-DFUR) for 14 days before surgery [27].
• METHODS: Expression of ERK-1 and ERK-2 protein was examined by Western blot in the breast cancer and normal breast (control) tissue of 48 patients, of whom 8 had received preoperative chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), with distribution of ERKs protein detected by immunohistochemical method [28].
• We confirmed that the enzyme activity of thymidine phosphorylase (TP) can substitute for 5'-deoxy-5-fluorouridine (5'-dFUR) sensitivity in clinical colorectal cancer (CRC) tissues [29].
• The present study shows that various cytokines such as tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interferon-gamma (IFN gamma) make tumor cells much more susceptible to the cytostatic 5'-deoxy-5-fluorouridine (5'-dFUrd) than to 5-fluorouracil (5-FUra) and other cytostatics [30].

Analytical, diagnostic and therapeutic context of Flutron

• PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy [2].
• Then, single chemotherapy with oral administration of 5'-deoxy-5-fluorouridine was initiated [31].
• Simultaneous occurrence of adenomas in stomach, duodenal bulb, and colon: disappearance of gastric and duodenal adenomas during oral administration of 5'-deoxy-5-fluorouridine [31].
• Interferon alpha and 5'-deoxy-5-fluorouridine in colon cancer: effects as single agents and in combination on growth of xenograft tumours [32].
• Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles (IV arm, n = 74) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles (oral arm, n = 92) [9].

References