Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:37076-68-9 (Tegafur)
 366 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.
J Med Chem 1977 Dec
PMID:Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers. 33

Twenty-six evaluable patients with disseminated or locally unresectable pancreatic or biliary tract carcinoma received Ftorafur (4 g/m2 iv day 1 and 22 and 2 g/m2 iv day 4 and 26), Adriamycin (60 mg/m1 IV day 1 and 45 mg/m2 iv day 22) and BCNU (150 MG/M2 IV DAY 1) combination chemotherapy (FAB) repeated at 6--8 week intervals. Two (29%) complete and one (14%) partial remissions were observed in 7 patients with biliary carcinoma while 5 of 19 (26%) patients with pancreatic carcinoma achieved partial remissions. Median survival for responding patients was approximately 11 months (range 7--16+) with median survivals of about 6 months (p less than 0.05 and about 3 months (p less than 0.05) for patients with stable and progressive disease. Major drug toxicity was myelosuppression with median lowest granulocyte counts of 1,000/microliters and platelet counts of 88,000/microliters. Approximately 25% of patients required antibiotic therapy for fever of unknown origin or documented infections. Other tolerable drug toxicities included nausea, vomiting and mucositis. The FAB regimen appears quite promising in biliary tract cancer and has efficacy in pancreatic carcinoma that warrants further clinical trials. Because of myelotoxicity observed with this regimen we now recommend a BCNU starting dose of 100 mg/m2 instead of 150 mg/m2.
Cancer 1979 Dec
PMID:Adriamycin, BCNU, ftorafur chemotherapy of pancreatic and biliary tract cancer. 38 4

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.
J Surg Oncol 1979 Dec
PMID:Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer. 39 97

1. Ftorafur, a fluorinated pyrimidine nucleoside antimetabolite, is metabolized by the beagle dog and rhesus monkey to 5-fluorouracil, which is subsequently biotransformed to the corresponding nucleosides, to alpha-fluoro-beta-ureidopropionic acid, to urea and to CO2. 2. In the dog, urea was the primary urinary metabolite while in the monkey, alpha-fluoro-beta-ureidopropionic acid predominated. 3. The dog and monkey excrete about 35 percent of the recovered dose as CO2. 4. The possibility that ftorafur is a relatively inactive transport form of 5-fluorouracil is discussed.
Xenobiotica 1977 Dec
PMID:The metabolism of ftorafur in the beagle dog and rhesus monkey. 41 63

We examined the effects and adverse drug reaction (ADR) of intermittent cisplatin therapy (ICDDPT) on advanced ovarian cancer patients (OCP). Most OCPs had undergone surgical removal of primary lesion and induction chemotherapy, and histopathological analysis indicated epithelial tumors. Five OCPs were stage III, six were stage IV and one stage II (n = 12). After surgical treatment and induction chemotherapy, ICDDPT was initiated with a 25-30 mg/day dose of CDDP for 5 days, every 3 months. During the intervals, maintenance immunochemotherapy of Tegafur and OK-432 was applied. Following ICDDPT, all patients except one are alive. The longest survival, to date is 5 years 7 months, while the decreased case survived 4 years. ADR was analysed according to the total dose of CDDP i.e. under 500 mg, over 500 mg-under 1,000 mg, 1,000 mg-under 1,500 mg, and 1,500 mg and over. Abnormal laboratory findings were observed for WBC, platelet (thrombocytopenia), Hb, GOT and GPT. The abnormal values except for GOT and GPT reverted to normal just before next administration. Thereafter ADR of CDDP with regard to the renal tubulus were studied by observing urinary NAG and urinary and serum beta 2 microglobulin. These values, however, were restored to within normal limits after 1 week of CDDP administration. These ADR were no greater with the increasing dose, such that accumulative toxicity was not observed. Study of the histological concentration of platinum showed a high level in liver tissue. Therefore, liver damage should be noted as on ADR of CDDP. In conclusion, ICDDPT for OCP was seen to be effective because of a good survival rate and low ADR.
Nihon Gan Chiryo Gakkai Shi 1990 Dec 20
PMID:[The effect on prognosis and the adverse drug reaction of intermittent cisplatin therapy in advanced ovarian cancer patients]. 207 85

Cultured L1210 murine lymphocytic leukemia cells were used to compare metabolic activation and cytotoxicity of 5-fluorouracil (FU), Ftorafur (FT), and three novel FU-sulfur analogues. These analogues, 1-(2'-tetrahydrothienyl)-5-fluorouracil (FUS), 1-(2'-tetrahydrothienyl)-5- fluorouracil-1'-oxide (FUSO), and 1-(2'-tetrahydrothienyl)-5-fluorouracil-1'-1'-dioxide (FUSO2), have yet to be fully evaluated for potential therapeutic value based on in vitro cytotoxicity. The role of these FU analogues as prodrugs was evaluated by comparing metabolism of normal pyrimidine pathways and activation by hepatic mixed function oxidases (MFO). Significant differences in biochemical activity and cytotoxicity were measured between FU and FU analogues. FU and FU analogues were cytotoxic to L1210 cells (63-92% growth inhibition of 100 microM concentrations after 72 hr of incubation). However, at equimolar concentration cytotoxicity of the FU analogues after MFO activation (56-66% growth inhibition) was greater than FU (47% growth inhibition). Hypoxanthine, a purine precursor, did not significantly alter fluoropyrimidine cytotoxicity with or without MFO. Thymidine and uridine, pyrimidine precursors, reduced FT and FUS cytotoxicities in the presence (27, 40%) and absence (25, 15%) of MFO but did not modify FU, FUSO, or FUSO2 cytotoxicities.
Pharm Res 1990 Dec
PMID:Cytotoxicity of three novel fluoropyrimidines in cultured L1210 murine lymphocytic leukemia cells. 209 68

A phase II trial of continuous oral therapy with UFT, a combination of uracil and the 5-fluorouracil analogue 1-(2-tetrahydrofuryl)-5-fluorouracil (Futraful, Ftorafur), was conducted in 40 patients with advanced colorectal cancer and 18 patients with advanced gastric cancer. Six partial responses were seen in the 36 evaluable patients with colorectal cancer (response rate 16.6%; 95% confidence limits 6.4-32.8%), and one partial response was seen in the 16 evaluable patients with gastric cancer (response rate 6%; 95% confidence limits 0.27-30.2%). The overall toxicity of the treatment was low, and all patients were treated as outpatients. The results suggest that oral UFT has comparable activity to standard regimes of 5-fluorouracil, and because of the convenience of oral administration is a useful therapy in the management of patients with advanced colorectal cancer.
Br J Cancer 1990 Dec
PMID:Phase II trial of UFT in advanced colorectal and gastric cancer. 225 7

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
Gan To Kagaku Ryoho 1990 Dec
PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71

An autopsy case of a 57-year-old man who had received cisplatin, total dose of 3,250 mg (1,920 mg/m2) after proctectomy for advanced rectal cancer with hepatic metastasis is reported. Platinum concentrations in autopsy tissue samples are also reported. Cisplatin at a dose of 20-40 mg was administered intravenously once a week for 82 weeks, but renal failure did not occur. The patient died 529 days after his last cisplatin therapy, due to acute suppurative cholangitis. On autopsy, the hepatic hilar metastasis involved the bile duct, but the other metastasis of the liver became regeneration and necrosis, and the kidneys showed few findings but congestion and arteriosclerotic change. The spleen evidenced mild hemosiderosis. Tissue samples obtained at the time of autopsy were assayed for platinum using flameless atomic absorption spectrometry. The spleen had the highest concentration, about 2.7 times as high as that of the liver. The liver, the heart and the kidneys had high platinum concentrations (greater than 3.04 micrograms/g), but those of the jejunum and the ileum were low (less than 0.95 micrograms/g). Although cisplatin, FT 207 and krestin were effective for the rectal cancer, platinum was undetectable (less than 0.13 micrograms/g) in the ascending and the transverse colons.
Gan To Kagaku Ryoho 1989 Dec
PMID:[An autopsy case of rectal cancer receiving cisplatin at total dose of 3.250 mg and platinum concentrations in autopsy tissue samples]. 259 63

We evaluated the anticancer effect of UFT, which is composed of 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur) and uracil in a molar ratio of 1:4, for prostatic carcinoma (DU-145) in nude mice, and the effect of 5-fluorouracil (5-FU) in vitro. Tumor growth of DU-145 in nude mice was inhibited in the group administered UFT (20 mg/kg), but was not in the Tegafur (100 mg/kg) group in comparison with the control group. The concentration of 5-FU in the tumor reached higher levels in the group administered UFT in comparison with the Tegafur group. Also, DU-145 cells were inhibited by about 70% in 4 gamma concentration of 5-FU compared with the control. These data suggest the clinical usefulness of UFT for prostatic carcinoma.
Gan To Kagaku Ryoho 1986 Dec
PMID:[Experimental study of UFT in prostatic carcinoma (DU-145) in nude mice]. 309 82


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