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At least 577 records · Page 32Linked to original sources
PubMed2006

[The effect of topical application of 5-fluorouracil on patency times after incisional myringotomy of guinea pig tympanic membrane].

OBJECTIVES: We investigated the effect of topical application of 5-fluorouracil after incisional myringotomy on the patency time and its use as an alternative to ventilation tube insertion. MATERIALS AND METHODS: Experimental tympanic membrane perforations were induced in two groups of guinea pigs. One group (20 tympanic membranes) was treated with a 50 mg/ml 5-fluorouracil-soaked sponge over the perforation for five minutes while the other (16 tympanic membranes) with saline-soaked sponges for the same duration. The patency times, otorrhea, and other complications were recorded. RESULTS: The mean patency of tympanic membrane perforations following incisional myringotomy was significantly longer in the 5-fluorouracil-treated group (11.3 days vs 7.0 days; p<0.01). None of the ears exhibited permanent perforation. CONCLUSION: The length of patency provided by 5-fluorouracil is not sufficient for optimal ventilation time in otitis media with effusion. However, in circumstances in which shorter patency times may provide sufficient ventilation, 5-fluorouracil application may be an alternative to ventilation tube insertion.

Administration, Topical↗
PubMed1987

Biochemical modulation of fluorouracil therapy in advanced colorectal cancer.

Fluorouracil has been the mainstay of chemotherapy in colorectal cancer for many years. We report our experience using fluorouracil in combination with other drugs which may modulate the spectrum of activity. Patients have been treated with allopurinol and fluorouracil and with two schedules of methotrexate and fluorouracil. We discuss other possible approaches to modulate fluorouracil action.

Allopurinol↗
PubMed1987

Permeability of latex and polyvinyl chloride gloves to fluorouracil and methotrexate.

The permeability of latex surgical and polyvinyl chloride (PVC) examination gloves to fluorouracil and methotrexate was studied using a radiotracer method. Drug-tracer solutions for both drugs were prepared by combining tritiated fluorouracil or methotrexate with fluorouracil or methotrexate injection, respectively. Drug-free solutions were also prepared to be as similar as possible to the vehicles of the commercial injections. Each half of a total of 40 equilibrium-dialysis cells (20 for each glove type) was filled with either the drug-tracer solution or the drug-free solution. The cell halves were then sealed with glove membranes cut from each type of glove and fastened together so that the drug-tracer and drug-free solutions of each respective drug were opposite one another. Samples were collected after 5 to 45 minutes from each dialysis-cell well and analyzed for drug using liquid scintillation counting techniques. Microgram levels of both drugs were detected in the drug-free dialysis wells for both glove types at each sampling time. Except for the methotrexate drug-labeled well sealed with the PVC glove membrane, the amount of drug in the dialysis wells was significantly different at different sampling times. The variability in results using gloves from different lots was also significantly different for both types of gloves. Overall, latex gloves were significantly less permeable than PVC gloves to fluorouracil, and PVC gloves were significantly less permeable to methotrexate than latex gloves. The latex and PVC gloves used in this study both exhibit time-dependent permeability to fluorouracil and methotrexate.(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis↗
PubMed1986

Sampling for airborne fluorouracil in a hospital drug preparation area.

Fluorouracil content was studied in air samples from a hospital pharmacy work area where a vertical laminar-airflow biological safety cabinet (BSC) vented into the work area was used for the preparation of antineoplastic drugs. The BSC was run 24 hours per day and used approximately 6 hours per day. During one 56-hour period and one 95-hour period, a portable pump delivering room air at 2 L/min was positioned 12 inches outside the BSC. Fluorouracil content in extracts from 0.5-micron Teflon filters housed in the pump was assayed by high-performance liquid chromatography. The assay's lower limit of fluorouracil detection was 0.2 ng/cu m air. In the 56-hour sampling period and the 96-hour sampling periods, 25.4 g and 25 g, respectively, of fluorouracil were prepared. No fluorouracil was detectable in the filter extracts. Use of an appropriate biological safety cabinet in conjunction with good aseptic technique and the recommended procedures for safe handling of antineoplastic drugs may reduce the potential for dispersal of drug into the pharmacy workroom environment.

Air Pollutants, Occupational↗
PubMed1986

Prophylactic topical 5-fluorouracil following treatment of human papillomavirus-associated lesions of the vulva and vagina.

Ninety patients were studied in a controlled, randomized fashion to evaluate the effectiveness of topical 5-fluorouracil in reducing the recurrence rate of human papillomavirus-associated lesions of the vulva and vagina. Following complete ablation of the lesions by one or more treatment modalities, 45 patients applied a single dose of 5% 5-fluorouracil cream biweekly to the vagina and/or vulva for at least six months. Forty-five patients used no prophylactic 5-fluorouracil cream. Patients in both groups were comparable with regard to race, age, and immune status, as well as the number, location, duration, clinical appearance, histology, and prior treatment of the lesions. Six patients (13%) with 5-fluorouracil prophylaxis and 17 (38%) without additional treatment (P less than .01) developed recurrent lesions during a follow-up time of nine to 22 months (mean = 14.4 months). Maintenance therapy with 5-fluorouracil was most effective in women with multiple lesions, multiple organ involvement, or with a depressed immune system.

Administration, Intravaginal↗
PubMed1984

[Effectiveness of 5-fluorouracil combined with hormones in low dose as a basal treatment for prostatic carcinoma].

In the treatment of prostatic carcinoma, administration of some therapeutic agents, e.g. hormones, continuously as a basal treatment, and other proper treatment, e.g. irradiation or chemotherapy or both, were combined for occasional recurrence of the disease as additional treatment. Effectiveness of 5-fluorouracil in combination with hormones (estrogen or gestagen) in low doses, as a basal treatment, was compared with that of hormones alone in high doses. 5-Fluorouracil at 200 mg/day doses combined with gestagen (allylestrenol or chloromadinone acetate) at 50 mg/day doses was compared with estrogen (hexestrol) at 60 mg/day doses in 30 randomized patients with previously untreated prostatic carcinoma. On the other hand, 5-fluorouracil at 200 mg/day doses combined with hexestrol at 30 mg/day doses was compared with hexestrol at 60 mg/day doses also in 26 randomized patients with carcinoma already well controlled by hexestrol at 60 mg/day doses for more than two years. In patients of the former group treated with 5-fluorouracil and gestagen the rate of recurrence was 20%, mean effective period of therapy was 69 months and 5-year survival rate was 73%, although, in patients treated with high dose estrogen, the rate of recurrence was 60%, mean effective period was 43 months and 5-year survival rate was 55%. At occasional recurrence of the disease, in nearly half the patients in both groups, the disease responded to additional treatments and remission was obtained again. In patients of the latter group with already well controlled disease, no significant difference in prognosis was observed between patients treated with 5-fluorouracil plus low dose estrogen and those treated with high dose estrogen alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Stability of fluorouracil in plastic containers used for continuous infusion at home.

The stability of fluorouracil when prepared and stored in plastic containers used for continuous infusion in home therapy was studied. Fluorouracil was diluted with 5% dextrose injection. Samples were stored for 16 weeks at 5 degrees C and room temperature in polyvinyl chloride drug reservoirs and at 5 degrees C in elastomeric balloons used in a disposable drug pump. Periodically, samples were tested by a stability-indicating high-performance liquid chromatography (HPLC) assay. At 5 degrees C, there was no significant degradation. At room temperature, there was a progressive increase in fluorouracil concentration, presumably because of evaporation of water. A 10% change in the fluorouracil concentration over 55 days was predicted. Fluorouracil is stable in 5% dextrose injection for at least 16 weeks when stored at 5 degrees C in the two types of containers studied.

Bromouracil↗
PubMed1978

Pharmacokinetics of fluorouracil in humans.

A high-pressure liquid chromatography method has been used to investigate the pharmacokinetics of fluorouracil after single i.v. doses to patients. The method is simple and is specific for fluorouracil. No interference was observed in fluorouracil determinations due to other administered medication. Plasma levels of fluorouracil declined rapidly after dosing. The mean half-life was 11.4 min, and drug was essentially cleared from plasma in 1 hr. Individual differences in plasma fluorouracil levels, and also in derived pharmacokinetic constants, were considerably less than those reported previously.

Adult↗
PubMed1982

Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture.

The cytokinetic and biochemical effects of 5-fluorouracil and 5-fluorouridine were examined in a human colon carcinoma cell line (HT-29) in culture. Logarithmically growing cells were approximately 100 times more sensitive to the lethal effects of 5-fluorouridine than 5-fluorouracil as measured by colony formation in soft agar medium. A 2-hr exposure of cells to 10(-3) M 5-fluorouracil or 10(-5) M 5-fluorouridine produced a 2-log reduction in colony formation, a 31--33% inhibition of [14C]deoxyguanosine incorporation into DNA, and 30--40% inhibition of [3H]adenosine incorporation into total RNA. Increasing the duration of drug exposure to 24 hr produced a proportional reduction in the drug concentration required to produce similar biochemical and cytocidal effects. However, cell lethality produced by either drug did not correlate quantitatively with inhibition of DNA or RNA synthesis. Examination of nuclear rRNA and 4 S RNA synthesis by agarose gel electrophoresis following 2-hr and 24-hr exposure to 5-fluorouracil or 5-fluorouridine indicated that processing of rRNA was not impaired, rRNA synthesis was inhibited by 10--40%, and 4 S RNA synthesis was unaffected. In contrast to these results, measurements of the incorporation fo [3H]5-fluorouracil or [3H]5-fluorouridine into nuclear RNA showed that a significant correspondence existed between the amount of drug incorporated into nuclear RNA and cell lethality. These results indicate that the primary determinant of cell lethality in HT-29 cells is the degree of fluoropyrimidine substitution in nuclear RNA and not inhibition of either DNA or RNA synthesis.

Cell Nucleus↗
PubMed1980

Platelet production after administration of antiplatelet serum and 5-fluorouracil.

Although 5-fluorouracil induces relatively minimal thrombocytopenia in mice compared with antiplatelet serum, the ensuing rebound thrombocytosis is much greater. It also occurs several days later. Administration of 5-fluorouracil 24 hr after antiplatelet serum suppresses the increase in platelets produced by antiplatelet serum while the subsequent thrombocytosis is indistinguishable from that produced by 5-fluorouracil alone. It is concluded that the thrombocytosis that occurs after 5-fluorouracil originates from a class of primitive stem cells, or early megakaryocyte precursors, which are not killed by the drug. Thrombocytosis occurring after antiplatelet serum is derived from more mature precursor cells, which are sensitive to 5-fluorouracil.

Animals↗
PubMed1980

[Anatomical and functional changes of the human small intestine induced by 5-fluorouracil (author's transl)].

In 10 female patients with carcinoma the effect of a single dose of 5-fluorouracil on morphologic alterations of the small bowel mucosa, intestinal disaccharidase-activities and lactose-tolerance-test was studied pre- and 96 hours posttherapy. After having given a standard dose of 1,25-1,50 gr 5-fluorouracil intravenously ( = 22 mg per kilo body weight) histologic changes of the small bowel mucosa (slight edema and shortening of the villi) were noted only in 4 cases. In the other cases the small intestine showed no morphological alterations of the mucosa. In all patients the lactose-tolerance-test after therapy with 5-fluorouracil was not affected. Following the administration of 5-fluorouracil no reduction of intestinal disaccharidase activities (maltase, saccharase, lactase) was observed. As a consequence of our results we suppose, that a patient given a single dose of 5-fluorouracil intravenously needs no specific diet without milk or milk-products.

Adult↗
PubMed1979

Comparison of liquid- and gas-liquid chromatographic assays of 5-fluorouracil in plasma.

A liquid-chromatographic assay of 5-fluorouracil in plasma is described. Advantages of this procedure over gas chromatography are the simpler extraction procedure, elimination of the need for a derivitization step with silylating agents, and a 20-fold greater sensitivity. The minimum detectable concentration of 5-fluorouracil in plasma is 25 microgram/L. The enhanced sensitivity enabled measurement of the concentrations of 5-fluorouracil found in plasms of patients receiving continuous intravenous infusions of the drug; such concentrations are generally unmeasurable by gas-chromatographic methods. We compared liquid-chromatographic and gas-chromatographic measurements on 36 plasma samples obtained from patients after rapid intravenous injection of 5-fluorouracil. The resulting correlation coefficient was 0.97, with a regression slope of 0.94. The liquid-chromatographic method is free of interference from other cytotoxic agents, anti-emetics, and folate derivatives that are frequently combined with 5-fluorouracil therapy.

Chromatography, Gas↗
PubMedDate not supplied

5-Fluorouracil sensitive adenocarcinoma--a new experimental model in the rat.

Transplantable nitrosoguanidine-induced rat colonic carcinoma was transplanted into the liver of 49 rats in six different series during three years. Tumor growth in vivo was surveyed by repeated laparotomy at day eight and day seventeen, and 25 rats were treated with 5-fluorouracil (30 mg/kg body weight) once a day, between day 8 and day 17. Tumor take was one hundred per cent and the tumor growth rate was similar throughout the experimental period. No animals died due to treatment or due to progressive tumor growth. The animals treated with 5-fluorouracil revealed a 5 per cent weight loss compared to the controls but no other signs of health deterioration were observed. The tumors treated with 5-fluorouracil had a 70 per cent decrease of growth rate compared to control rats. Exposure of the tumor cells in vitro to 5-fluorouracil induced a dose--related decrease in surviving cells with a 50 per cent reduction of surviving cells 48 hours after exposure to 0.01 mg/ml of 5-fluorouracil. Thus, we present here a new, feasible and reproducible animal model, excellently suited to in vivo and in vitro studies of fluorinated pyrimidines and solid tumor growth.

Adenocarcinoma↗
PubMed1994

Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.

A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.

Acute Disease↗
PubMedDate not supplied

5-Fluorouracil and interferon-alpha in chemotherapy refractory bladder carcinoma: an effective regimen.

Seventy-seven patients with metastatic transitional cell carcinoma of the bladder who were unable to receive primary Cisplatin-based therapy or failed primary chemotherapy received one of three sequential 5-Fluorouracil-based salvage regimens: a) 5-Fluorouracil (1000 mg/m2 B.S.A. x 5 days) and Mitomycin-C (14 mg/m2 B.S.A. 6 week intervals), b) 5-Fluorouracil (750 mg/m2 B.S.A. x 5 days) and a-Interferon (5 miu/m2 B.S.A. daily x 5 then 3 times a week (TIW), c) 5-Fluorouracil (500 mg/m2 B.S.A. x 5 days), a-Interferon (5 miu/m2 B.S.A. x 5 days then TIW) and 13-Cis Retinoic Acid in escalating doses daily. Only 1 (6%) of the patients with regimen A responded, whereas 9 (30%) of the patients with regimen B and 8 (27%) in regimen C responded. Although all responses were partial remissions, responses were seen in patients with advanced and initially refractory transitional cell carcinomas. This data reveals that a-Interferon and 5-Fluorouracil is an effective combination in the treatment of metastatic transitional cell carcinoma and worthy of further study.

Adult↗
PubMed1996

[Three cases of lung metastases of renal cell carcinoma treated with a combination of interferon-alpha, 5-fluorouracil and leucovorin].

Three patients with lung metastases of renal cell carcinoma (RCC) were treated with a combination of interferon-alpha, leucovorin and 5-fluorouracil. All patients were male between 60 and 66 years and had been treated by nephrectomy prior to the combination therapy. Interferon-alpha was administered at the dose of 9 x 10(6) IU intramuscularly 3 times/week, leucovorin at 30 mg/m2 per day intravenously (day 1 to 5) and 5-fluorouracil at 500 mg/m2 daily by continuous infusion intravenously (day 1 to 5) followed by weekly bolus therapy. One patient achieved complete response for 17 months and the other two achieved stable disease for 6 and 16 months. Side effects related to this therapy were diarrhea, stomatitis, alopecia, leucocytopenia and thrombocytopenia. Grade 3 stomatitis occurred after the continuous administration of 5-fluorouracil in one patient; he recovered by discontinuation of 5-fluorouracil. Combination therapy with interferon-alpha, leucovolin and 5-fluorouracil might be effective for the treatment of lung metastases of RCC.

Aged↗
PubMed1977

Disposition of 5-fluorouracil after intravenous bolus doses of a commercial formulation to cancer patients.

A high-pressure liquid chromatographic method that is used to determine the pharmacokinetic disposition of 5-fluorouracil from the plasma compartment is presented. The method requires only 0.5 ml of plasma for each determination and is sensitive to 0.1 mg of drug per liter. Novel methodology with the use of an ion-specific electrode technique for the determination of urinary excretion kinetics of 5-fluorouracil and its metabolites is also presented. This study demonstrated a much greater variability for the disposition of 5-fluorouracil by cancer patients than has been reported previously. The apparent volume of distribution for this drug varied more than 37-fold. Its plasma half-life varied more than 19-fold, and its urinary excretion half-life varied almost 400-fold. These data are compatible with the hypothesis that this variation could account, at least in part, for the variable therapeutic and toxic response to 5-fluorouracil. The methodology presented in this study is sufficiently simple and sensitive to allow assessment of this hypothesis by investigating cancer patients who receive therapeutic doses of 5-fluorouracil.

Aged↗
PubMed1997

Dihydropyrimidine dehydrogenase activity in hepatocellular carcinoma: implication in 5-fluorouracil-based chemotherapy.

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents. Previous studies have demonstrated the clinical importance of determination of DPD in cancer patients, suggesting that the efficacy and toxicity of 5-fluorouracil may directly relate to the DPD activity in both tumor and host tissues. In the present study, DPD activity was determined in 50 pairs of tumor and uninvolved liver specimens in Chinese cancer patients with hepatocellular carcinoma. Mean enzyme activity in uninvolved liver tissues (0.45 +/- 0.02 nmol/min/mg protein) was significantly higher than that in tumor specimens (0.34 +/- 0.03 nmol/min/mg protein). Statistical analysis revealed no significant differences in DPD activity of tumor and uninvolved liver specimens among different age and gender groups. Compared to previously reported tumor studies, hepatomas were found to have relatively high DPD activity. Since high levels of DPD would be expected to metabolize 5-fluorouracil, these findings may provide an explanation for the relative 5-fluorouracil resistance of hepatoma and may have implications for designing a new therapeutic strategy such as modulation of 5-fluorouracil chemotherapy by DPD inhibitors.

Adult↗