Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.
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PMID:Phase I study of ftorafur, an analog of 5-fluorouracil. 120 38

Six patients with advanced renal cell carcinoma was treated with a new chemo-endocrine regimen consisting of Tegafur, Adriamycin, Methotrexate and Tamoxifen. Estrogen receptor was measured in four cases from renal or metastatic tumors by DCC method, presenting 14.7, 9.7, 1.0 and 0 f moles/mg protein respectively. The patients were medicated with 800-1,200 mg of Tegafur and 20 mg of Tamoxifen daily po, and 20 mg of Adriamycin and 10 mg of Methotrexate intermittently for two weeks interval iv. According to a criteria of Japan Society for Cancer Therapy, two were regarded as CR, one as PR, one as NC and two as PD. The one out of two cases with and without estrogen receptor responded favourably to this therapy. Side effects observed in the treatment were mild gastrointestinal disorders including nausea and vomiting, slight degree of leukopenia, stomatitis, pigmentation and liver dysfunction. The patients were found to be in good quality of life during the treatment because of less toxicity. This therapy can be regarded as a good modality for a treatment of advanced renal cell carcinoma. This is a first report of combined chemo-endocrine therapy with Tegafur, Adriamycin, Methotrexate and Tamoxifen for renal cell carcinoma in the world.
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PMID:[A combined chemo-endocrine therapy with tegafur, adriamycin, methotrexate and tamoxifen for advanced renal cell carcinoma]. 223 Apr 47

The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir in connection with first treatment cycle was on average seen on day 15 in patients receiving 5-FU and on day 28 in patients receiving Ftorafur. Significantly more patients on 5-FU developed stomatitis. There was no difference in the number of patients with diarrhea or nausea/vomiting. Median survival and response rates were not significantly different after the two treatment schedules.
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PMID:Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer. 312 9

We have treated 15 patients with advanced gastrointestinal carcinoma with a cyclical regimen of combined Ftorafur (N1-((2-furanidyl-))-5-Fluorouracil, a 5-FU pro-drug) and external beam radiation. The Ftorafur (FT) was administered orally in daily doses of between 1.0 and 2.5 g/m2/day in 3 divided doses in a Phase I format. The drug was given daily for 5 days along with conventional X ray treatment portals and daily radiation doses of 250 rad on each of the first 4 days of each treatment cycle. The patients were then rested for a minimum of 10 days or until all significant side effects had passed. The total number of 1,000 rad cycles and radiation dose were dictated by tolerance and by normal organ dose limitations. The most common toxicity in general, and the most common limiting toxicity was nausea and vomiting, in contrast to oral FT alone where diarrhea is more prominent. Stomatitis was seen only once and no other form of serious toxicity was encountered. Two-thirds of the patients responded in subjective terms (pain relief). There was 1 partial response to FT alone (pulmonary metastases outside the treatment field). The sole patient whose treatment field was outside the abdomen (chest portals for esophageal carcinoma) developed pneumonitis which contributed to his death. No other delayed effects were noted. Serum FT levels were related to the ingested dose and in the microgram range while serum 5-FU levels were in the nanogram range indicating slow decomposition of FT into 5-FU. The therapy was reasonably well tolerated at doses of 2.0 g/m2/day or lower with abdominal radiation. FT offers the potential for replacing intra-venous infused 5-FU as a clinical radiosensitizer.
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PMID:Phase I and pharmacologic study of oral ftorafur and X ray therapy in advanced gastrointestinal cancer. 391 71

A Phase II study of UFT for head and neck cancer was conducted in 10 institutions. UFT is a mixture of Futraful and uracil. Eighty-four patients entered this trial, of which 60 were evaluable. UFT was administered orally at a daily dose of 600 mg/day. Eight patients achieved complete response and 10 achieved partial response with an over-all response rate of 30.0 %. Evaluating response according to by histology, the response rate was 30.9% for cases of squamous cell carcinoma. Complete response was observed in one case of undifferentiated carcinoma. Response rate according to primary site was 33 to 40% for the nose & paranasal sinuses, mesopharynx, hypopharynx and larynx. The response rate was 28.9% for the group of patients treated previously, and 33.3% for the group previously untreated. The mean time for 50% or more regression of the tumor was 4.3 weeks. Toxic effects appeared in 40.3% of 67 evaluable cases as anorexia, nausea, vomiting, stomatitis, diarrhea etc. In one case of maxillary carcinoma, severe bone marrow suppression was observed. We concluded that UFT therapy was markedly effective for head and neck cancer.
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PMID:[Phase II study of UFT for head and neck cancer]. 392 39

A comparative, randomized trial was conducted to determine the efficacy of oral UFT (Tegafur and Uracil) versus 5-fluorouracil (5-FU) in combination with cyclophosphamide and doxorubicin in patients with metastatic breast cancer. Of 62 evaluable patients, 31 received UFT (350 mg/m2/day orally x 14 days), doxorubicin (50 mg/m2 intravenously [I.V.] day 1) and cyclophosphamide (500 mg/m2 I.V. day 1). The other 31 patients received 5-FU (500 mg/m2 I.V. days 1 and 8), doxorubicin (50 mg/m2 I.V. day 1), and cyclophosphamide (500 mg/m2 I.V. day 1). Regimens were repeated for a total of six cycles. The two groups were comparable in terms of age, gender, performance status, menopausal status, and number and sites of metastases. No statistical difference in overall response rates was seen (UFT arm, 48.4% vs. 5-FU arm, 35 %; p = 0.30). Median response duration was 16 weeks (range, 4-30) for both arms. The toxicity profile (alopecia, anemia, leukopenia, thrombocytopenia, diarrhea) was similar in both groups and both regimens were well tolerated. Anemia and stomatitis were significantly more common in the 5-FU arm (p = 0.02). Thus, oral UFT has response rates and duration of response that are comparable to 5-FU in a combination regimen for advanced breast cancer.
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PMID:A comparative, randomized trial of UFT and 5-fluorouracil in combination with cyclophosphamide and doxorubicin in the treatment of advanced breast cancer patients at The Philippines General Hospital. 897 77

Following p.o. administration to rats bearing advanced colorectal carcinoma, Ftorafur (FT) is converted to 5-fluorouracil (FUra) by microsomal P450 in the liver. To optimize the therapeutic selectivity of the FUra generated from FT, three approaches were utilized: (a) inhibition of FUra degradation to dihydrofluorouracil by uracil as an alternative substrate for uracil reductase in the molar ratio of 4 uracil:1 FT (UFT); (b) modulation of drug inhibition of thymidylate synthase by leucovorin (LV); and (c) by increasing the level of FUra incorporation into cellular RNA by N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartate transcarbomylase. The maximum tolerated dose (MTD) of FT and UFT, administered 3 times a day for 28 days, was 150 mg/kg/day and 60 mg/kg/day, respectively. The MTDs were not significantly modified by LV (150 or 600 mg/kg/day), administered by the p.o. route with the drugs, or by PALA (100 mg/kg) administered weekly by the i.v. route. The dose-limiting toxicity of FT alone and in combination with the modulators was stomatitis. The severe alopecia observed with FT alone was reduced significantly by uracil. At the MTD, the antitumor activity of UFT was superior to those of FT and FUra alone and in combination with LV and/or PALA. The 3-month sustained complete tumor regression for UFT, FT, and FUra was 38%, 0%, and 13% (for the weekly schedule), respectively. Although uracil, LV, and PALA individually increased the antitumor activity of FT at its MTD, the combination of the three modulators produced the highest therapeutic efficacy in rats bearing advanced colorectal carcinoma, in which 100% of the treated animals achieved complete and sustained tumor regression. The therapeutic efficacy observed with FT modulation could not be achieved with FUra administered by different schedules, each at its MTD alone or in combination with either LV or PALA. In brief, modulation of FT produced greater therapeutic efficacy and selectivity than FUra. Furthermore, the combined use of modulators capable of inhibiting the degradation pathway of FUra and potentiating the effects of the anabolic metabolites action appears to offer the greatest therapeutic potential.
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PMID:5-Fluorouracil prodrug: role of anabolic and catabolic pathway modulation in therapy of colorectal cancer. 981 53

Tegafur is a prodrug of the antineoplastic agent fluorouracil, and is administered in a 1:4 molar ratio with the fluorouracil modulator uracil. Oral tegafur/uracil 300 mg/m(2)/day plus calcium folinate 75 or 90 mg/day for 28 days every 35 days was as effective as intravenous (IV) fluorouracil 425 mg/m(2)/day plus folinic acid 20 mg/m(2)/day for 5 days every 28 or 35 days in the treatment of patients with metastatic colorectal cancer in two large, randomised, nonblind, multicentre trials (n = 816 and 380). Median survival time among patients treated with tegafur/ uracil or fluorouracil was approximately 12 months in both trials. Results from both trials also demonstrated no significant between-group differences in overall response rates among patients treated with oral tegafur/uracil (12 and 11%) or IV fluorouracil (15 and 9%). In elderly patients (aged > or = 70 years) with metastatic colorectal cancer, results from small noncomparative studies showed that treatment with oral tegafur/uracil afforded overall response rates of 12.5 to 29% and was well tolerated. During preoperative treatment with oral tegafur/uracil plus calcium folinate as an adjunct to radiotherapy in patients with stage II or III rectal cancer, the maximum tolerated dosage of tegafur/uracil was 350 mg/m(2)/day (administered 5 days per week for 5 weeks). Among the 15 patients who were followed for 5 to 8 months, three had a complete response to treatment. Treatment with tegafur/uracil was also given postoperatively. The most common adverse events associated with oral tegafur/uracil were anaemia, nausea/vomiting, diarrhoea, thrombocytopenia, mucositis, neutropenia, asthenia, anorexia and abdominal pain. Oral tegafur/uracil was associated with a significantly more favourable tolerability profile than IV fluorouracil in the two large randomised trials. In particular, stomatitis and most adverse haematological events were less frequent.
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PMID:Oral tegafur/uracil. 1188 48

The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.
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PMID:Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer. 1550 21