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At least 19 recordsLinked to original sources
PubMed2001

Rat cytochrome p450 1A and 3A enzymes involved in bioactivation of tegafur to 5-fluorouracil and autoinduced by tegafur in liver microsomes.

Tegafur, an anticancer prodrug, is reported to be bioactivated to 5-fluorouracil (5-FU) by cytochrome P450 (P450) enzymes. Liver microsomal P450 enzymes involved in the biotransformation of tegafur into 5-FU in rats and the effect of tegafur in vivo on P450 levels in rats were investigated. Of 12 cDNA-expressed rat P450 enzymes tested, CYP1A2, CYP3A1, and CYP2C11 had high 5-FU formation rates from 100 microM and 1.0 mM tegafur concentrations. The contributions of CYP1A, CYP2C, and CYP3A enzymes to 5-FU formation in male rat liver microsomes were supported by immunoinhibition studies. 5-FU formation from tegafur, at substrate concentrations of 100 microM and 1.0 mM, was increased by intraperitoneal treatment of tegafur (50 mg/kg for 5 days) as well as by beta-naphthoflavone, phenobarbital, and dexamethasone. Orally administered tegafur (100 mg/kg daily for 20 days) caused the induction of CYP2B (5-fold) and of CYP1A and CYP3A (approximately 2-fold) and of 5-FU formation (approximately 2-fold) in rat liver microsomes. These results suggest that CYP1A and CYP3A enzymes, autoinduced by tegafur, have important roles in 5-FU formation from tegafur in rat liver microsomes. Coadministration of tegafur and P450-inducing drugs could markedly enhance the biotransformation of tegafur into 5-FU via P450 induction.

Animals↗
PubMed1986

In vitro release of tegafur from a fatty-base suppository and in vivo bioavailability of tegafur.

This study was designed to determine the in vitro release of tegafur from a suppository and the in vivo bioavailability of tegafur in rats. Two different suppository preparations (product A-1 and product A-2) containing 750 mg of tegafur were tested for in vitro release of tegafur by the Muranishi Method (membrane diffusion method) and the partially modified paddle method (permeability through dialysis tubing). When determined by either method, the amount of tegafur released from product A-2 during the whole experimental period was significantly greater than that released from product A-1. When tested by the Muranishi method, however, the difference in the amount released during the first 10-min period was not significant. A greater bioavailability of tegafur after rectal administration was obtained by product A-2 more than product A-1. A significant correlation was observed between the in vitro release and the in vivo bioavailability. The present results indicate that there are considerable differences in physiochemical characteristics between product A-1 and product A-2.

Animals↗
PubMed1989

[Serum and tissue concentration of tegafur and 5-FU after administration of tegafur suppository in patients with lung cancer--correcting the influence of residual blood in the tissue].

Tissue concentration of tegafur and 5-FU was studied in 25 patients with of primary lung cancer, given 2 x 750 mg of tegafur suppository daily preoperatively (total doses 3.75-9.75 g, mean 5.16 g). Furthermore, the influence of blood remaining in the tissue was corrected in the determination of tegafur and 5-FU concentration. The tegafur level in tumor tissue (9.614 +/- 5.739 micrograms/g) was significantly (p less than 0.01) low compared with those in serum and normal lung tissue (13.185 +/- 8.198 micrograms/ml, 12.954 +/- 10.048 micrograms/g). On the other hand, the 5-FU level in tumor tissue (0.124 +/- 0.208) was significantly (p less than 0.01, p less than 0.05) high compared with those in serum and normal lung tissue (0.019 +/- 0.013 micrograms/ml, 0.035 +/- 0.031 micrograms/g) and showed approximately 2.5 times more minimum effective concentration against tumor cells (0.05 micrograms/g). The results show that preoperative administration of 2 x 750 mg of tegafur suppository daily is effective for the transfer of tegafur and 5-FU to lung cancer tissue.

Adult↗
PubMed1982

[Sequential changes in blood concentrations of tegafur and 5-FU during oral administration of fine granules of tegafur in patients with primary liver cancer].

Tegafur fine granule preparation orally administered to the patients with primary hepatoma and liver cirrhosis, and the concentration of tegafur and 5-fluorouracil in the blood were determined. The concentration of tegafur in blood was maintained well in the injured liver, and remained same 3 weeks after administration of tegafur fine granules. The concentration of 5-fluorouracil in the blood decreased distinctly when the dysfunction of the liver was severe (KICG less than 0.070). In the case of malignant disease with the injured liver, oral administration or tegafur might be less effective. However, the concentration of 5-fluorouracil in the blood did not decrease 3 weeks after administration of tegafur fine granules. No cases showed noticeable clinical effects by only oral administration.

Administration, Oral↗
PubMed1984

[Thermotherapy for cancer of the urinary bladder in combination with tegafur and picibanil--with special reference to the serum bladder and bladder cancer tissue concentrations of tegafur in a perfusion fluid].

Thermotherapy combined with Tegafur and Picibanil was performed in 32 patients with cancer of the urinary bladder. The thermotherapy was performed with a closed circulation type of thermotherapeutic apparatus manufactured for trial, using a 3-way catheter. The flow quantity of the perfusate was 150 ml/min at a constant temperature of 43 degrees C. The temperature was monitored at the inlet and outlet catheter at the urethral meatus. The thermotherapy was performed for 6 hours once a week. Tegafur and Picibanil were added to the perfusate at the time of thermotherapy. No anesthesia was used. Complete disappearance of tumor occurred in 9 cases. The concentration of Tegafur in the serum, tumor and bladder wall was simultaneously measured. The serum levels after two hours of thermotherapy with 16 gm of dissolved Tegafur showed that FT-207 was 28.837 mcg/ml and 5-FU, 0.028 mcg/ml. After 4 hours the FT-207 was 36.464 mcg/ml and 5-FU, 0.040 mcg/ml. By the 6th hour FT-207 was 39.430 mcg/ml and 5-FU, 0.049 mcg/ml. After 24 hours FT-207 was 11.242 mcg/ml and 5-FU, 0.013 mcg/ml in the serum, while FT-207 was 8.205 mcg/g and 5-FU, 0.274 mcg/g in the bladder tumor, and FT-207 was 17.029 mcg/g and 5-FU, 0.157 mcg/g in the bladder wall. Nausea was observed in 1 case in which a large quantity of Tegafur was absorbed. No other side effects were noted.

Aged↗
PubMed1994

Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1:4 tegafur and uracil combination.

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, were examined in 26 patients with macroscopic Stage I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28 +/- 26.88, 4.41 +/- 1.78, and 0.51 +/- 0.20 micrograms h ml-1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.

Administration, Oral↗
PubMed1985

[Thermotherapy for cancer of the urinary bladder in combination with tegafur suppository and picibanil--concentrations of tegafur in the serum and tissues in bladder carcinoma].

Thermotherapy combined with tegafur (FT-207) and Picibanil was performed in 13 patients with cancer of the urinary bladder. The thermotherapy was performed using a closed circulation type of thermotherapeutic apparatus manufactured for this experiment, by way of a 3-way catheter. The flow rate of the perfusate was 150 ml/min at a constant temperature of 43 degrees C. The temperature was monitored at the inlet and outlet catheter of the urethral meatus. The thermotherapy was performed for a 6-hour period once a week. A tegafur 3000-mg suppository was given 2 hours before the thermotherapy, and Picibanil was added to the perfusate at the time of thermotherapy. No anesthesia was used. Complete disappearance of the tumor was observed in 1 case. The concentrations of tegafur in the serum, tumor and bladder wall were measured simultaneously. The levels obtained at two hours after rectal administration of the tegafur 3000-mg suppository were 19.420 mcg/ml for FT-207 and 0.025 mcg/ml for 5-FU in the serum, 13.170 mcg/g for FT-207 and 0.140 mcg/g for 5-FU in the bladder tumor, and 20.447 mcg/g for FT-207 and 0.252 mcg/g for 5-FU in the bladder wall. Eruption was observed in 1 case. No other side effects were noted.

Adult↗
PubMed1991

A cooperative randomized study on tegafur plus mitomycin C versus combined tegafur and uracil plus mitomycin C in the treatment of advanced gastric cancer.

A randomized controlled trial involving 13 institutions in Japan was conducted in order to compare the efficacy of tegafur plus mitomycin C (MMC) (Regimen A) and UFT (a combination of uracil and tegafur at a molar ratio of 4 to 1) plus MMC (Regimen B) for patients with advanced gastric cancer, who had not received any prior cancer chemotherapy. Regimen A (tegafur + MMC) consisted of 5 mg of MMC/m2/week given intravenously, and 500 mg of tegafur/m2/day given orally. Regimen B consisted of the same schedule of MMC and 375 mg of UFT/m2/day given orally. One hundred and eighty-six patients with primary gastric cancer were entered; 183 were eligible and 3 were ineligible for the study. A total of 169 were evaluable for efficacy of the treatment, including 90 patients with Regimen A and 79 with Regimen B. A response rate of 7.8% (7/90 cases) for Regimen A and one of 25.3% (20/79 cases) for Regimen B were obtained, indicating a significantly higher response rate for Regimen B according to the Criteria for Evaluating Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer (P = 0.004). Regarding side effects, no marked differences in either severity or incidence were observed between the two groups. The group assigned to Regimen B showed a significant survival advantage after adjustment for major prognostic factors using a proportional hazards model (P = 0.0398). Moreover, a close correlation of antitumor effect and survival duration was found when the above criteria were used.

Administration, Oral↗
PubMed1994

Multicentre randomised study of adjuvant chemotherapy with mitomycin C and tegafur or tegafur-uracil in gastric cancer.

OBJECTIVE: To compare therapeutic results and five year survival after two regimens of adjuvant chemotherapy after resections for gastric cancer. DESIGN: Prospective randomised multicentre trial. SETTINGS: 21 departments of surgery. SUBJECTS: 243 patients with stage II, III, or IV gastric cancer. INTERVENTIONS: All patients received an intravenous bolus of mitomycin C 20 mg on the day of operation, and 10 mg on the first postoperative day. They were then randomised to receive either tegafur 600 mg or tegafur-uracil 600 mg orally daily beginning two weeks after operation and continuing for two years. Patients with histological confirmed stage IV disease also received mitomycin C 10 mg every three months starting one month after operation. MAIN OUTCOME MEASURES: Survival and side effects. RESULTS: 13 patients (5%) were withdrawn from the study, leaving 230 for analysis. There were no serious side effects and both drugs were safe when given continuously for two years. There were no significant differences in 5 year survival (though patients who were given tegafur-uracil tended to live longer), except when patients who had histological curative resections were compared with and those with poorly differentiated adenocarcinoma (p = 0.04).

Adult↗
PubMed1987

[Serum concentration of 5-FU and tegafur (FT-207) after administration of tegafur (FT-207) suppository with the colostomy].

Tegafur (FT-207) suppositories were administered at a rate of 750 mg via the artificial anus (ST Group) following surgery of rectal cancer. Comparative studies were conducted of changes in blood concentrations of 5-FU and tegafur at the time of initial administration and following one week of continuous use for the low-anterior resection cases (LA Group) and the rectal administration cases (RE Group). FT-207 concentration at initial administration was low in the ST group compared to those for both LA and RE groups which received anal administration of the drug, but only little changes were noted. Blood concentration one hour after administration was 11.1 micrograms/ml, elevated to 14.3 micrograms/ml at two hours, and remained at 10 micrograms/ml and above for six hours following administration. The ST group 5-FU concentrations at two, four and six hours after administration were significantly lower than those in the RE group but the changes were little. Blood concentrations were 0.015 microgram/ml at one hour after administration, 0.017 micrograms/ml at two hours and maintained virtually the same level thereafter. An effective concentration of 0.012 microgram/ml was maintained even at ten hours following administration. After one week of administration of the suppositories, the ST group showed the lowest concentration among three groups, but it was approximately double compared to the initial concentration; FT-207 showed nearly the same concentration in the LA group and 5-FU blood concentration was 0.025 microgram/ml at one hour after administration, reached to a maximum of 0.030 microgram/ml at two hours and maintained 0.020 microgram/ml and higher at ten hours. 5-FU concentration in the LA and RE groups after one week of continuous administration showed a dual-peaked pattern. No patient with an abnormal artificial anus was involved in this study. The artificial anus is thought to be an adequate and effective administration route of FT-207 suppositories.

Adult↗
PubMed1995

[Neoadjuvant chemotherapy with tegafur suppository for rectal cancer--effects of tegafur on nuclear DNA content of cancer cells--Tochigi Colorectal Cancer Study Group].

To assess the significance of neoadjuvant chemotherapy for large bowel cancer, we investigated an effect of tegafur on cancer cell kinetics by DNA content flow cytometric analysis. The pathologic specimens analyzed in this study were obtained from 28 patients with rectal cancer who had received tegafur suppositories prior to surgery. Mean cumulative doses administered were 13.4 g, and mean duration was 12.7 days. In 24 of the 28 specimens, the DNA ploidy and DNA index of the cancer cells were essentially unchanged after the chemotherapy, and DNA aneuploidy was present in 67%. The proportion of cells in S-phase in DNA aneuploid tumors was significantly higher than in DNA diploid tumors. The proportion of cells in G0G1-phase was inversely correlated to that in S-phase. After the chemotherapy, the proportions of cells in S-phase increased both in DNA diploid and aneuploid tumors, although a significantly higher mean value was found only for the latter (p < 0.05). In the DNA aneuploid tumors, there was a higher frequency of responders confirmed by histological evaluation (44%) as compared to the DNA diploid tumors (25%), and a tendency for increases in S-phase fraction of the responders to be greater than in non-responders. These results suggest that DNA flow cytometry-derived parameters may conceivably be useful in predicting the antitumor effect of 5-FU and its derivatives against large bowel cancer.

Aged↗
PubMed1989

[Comparative study of tegafur (p.o.) and mitomycin C (MMC) plus tegafur in cases of unresectable gastric cancer].

Sixteen cases of gastric cancer with liver metastases (H2 less than) as group A, fifteen with distant peritoneal metastases (P2 less than) as group B, twenty-five with distant lymph nodes metastases (N3 less than) as group C, twenty-eight with two prognostic factors as group D, and seven with three factors as group E were treated. A1, B1, C1, D1 and E1 groups were treated with mitomycin C (MMC) (4 mg) + tegafur (FT) (400 mg) (i.v.-weekly) and A2, B2, and C2 group with FT (600 mg) (p.o.-daily). Partial response in the evaluable cases was found in 7 cases and a total response rate was 11.7%. The 50% survival interval was as follows; 8.5 months (M) in A1 group, 10.0 M in A2, 7.2 M in B1, 2.3 M in B2, 10.4 M in C1, 14.2 M in C2, 5.2 M-7.2 M in D1, and 3.1 M in E1. In the cases with H2 less than or N3 less than, FT (p.o.) and with P2 less than, MMC + FT (i.v.) were effective respectively. Chemotherapeutic effect was better in A1 and A2 group from the aspects of prognostic factors and in the cases of poorly differentiated adenocarcinoma from histological types than in B1 and B2 group and well or moderately differentiated adenocarcinoma.

Adenocarcinoma↗
PubMed1988

[Effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of Tegafur and UFT (Tegafur plus uracil)].

The effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of 1-(2-Tetrahydrofuryl)-5-fluorouracil (Tegafur; FT) and FT plus uracil (UFT) was examined by using nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed a palpable tumor 17 days after KF cell inoculation unless treatment was done. A combination of UFT and calmodulin antagonists (W-5 or W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volume in the treatment groups combined with calmodulin antagonists was significantly less than in those in the untreated group after 31 days of tumor inoculation. In addition, tumor volume in a UFT plus W-7 treated group was significantly less than those not only in the untreated group but also in the UFT alone, FT alone, W-5 alone and W-7 alone treated groups, suggesting a synergistic inhibitory effect on tumor growth. The longest median survival time was also observed in a UFT plus W-7 treated group. 5-Fluorouracil (5-FU) content in the tumor of groups treated with FT plus W-5 or W-7 was similar to that in a group treated with FT alone. On the other hand, that of a group treated with UFT plus W-7 was about 2-fold higher than that of a UFT -only treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A double blind comparative study of tegafur (FT) and UFT (a combination of Tegafur and uracil) in advanced breast cancer.

A double blind study to compare the efficacy of oral UFT (400 mg Tegafur (FT) plus 896 mg uracil/day) with that of oral FT (800 mg/day) on advanced breast cancer was performed between November, 1986, and November, 1989. Sixty patients were registered for the trial and fifty-six cases were evaluated (28 for UFT and 28 for FT). The primary end points in the study were response rate and time to relapse. There were no significant differences in patients' characteristics in either group. The objective response rates were 39% (11/28; 95% confidence interval (C.I.), 22-59%) in UFT and 21% (6/28; 95% C.I., 8-41%) in FT, without statistical significance (P = 0.25). For time to relapse, a trend was seen in favor of UFT, but this effect did not achieve statistical significance (P = 0.09). Both subjective and objective adverse effects were similar between the two treatments. The overall survivals were similar in both parts of the study. The size of the trial was too small for a definite conclusion to be drawn although, for both response rate and time to relapse, a trend was seen in favor of UFT. A large scale randomized study will be necessary to compare the drugs in the management of patients with advanced breast cancer.

Adult↗
PubMed1989

[Long-term administration of tegafur in postoperative adjuvant chemotherapy in gastric cancer patients. Serial analysis of serum tegafur and 5-fluorouracil concentrations, and influence from PSK combination].

We investigated the pharmacokinetics of long-term (2-year) daily oral administration of FT-207-E or UFT for postoperative adjuvant chemotherapy in 85 gastric cancer patients by measuring serum FT-207 and 5-FU concentration serially. There were no significant changes in serum FT-207.5-FU concentration during observation period between FT-207-E and UFT groups. There was different operative modality between partial gastrectomy (Billroth I) and total gastrectomy, but no significant difference in serum FT-207.5-FU concentration between the two groups, and no significant serial changes in serum FT-207.5-FU concentrations were observed in both groups. Conversion from FT-207 to 5-FU measured by serum concentration was not suppressed by combination with the biological response modifier PSK.

Adjuvants, Immunologic↗