Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.
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PMID:[High-dose Tegafur (FT) for primary lung cancer: a phase I trial]. 201 1

A phase I clinical study of tegafur (ftorafur) was conducted in 29 patients with various advanced solid tumors. To evaluate its efficacy and toxicity, the initial dose of 0.5 g/m2/day x 21 days at 3-week intervals was progressively increased to a maximum dose of 1.5 g/m2/day. Tegafur was administered orally in two or three divided doses. Diarrhea was the dose-limiting toxic effect and occurred more often in patients with abnormal pretreatment liver function. Nausea occurred in about one-half of the patients, but vomiting was infrequent. Skin rash and mucositis occurred in 10% and 7% of the patients, respectively. Neurologic toxic effects of tegafur were infrequent and mild. The hematologic toxicity of tegafur was minimal. Antitumor activity could be evaluated in 21 patients with measurable disease. One complete and three partial responses were observed in four of 17 patients who had adenocarcinoma of unknown primary origin. All responses occurred at doses greater tan or equal to 1.0 g/m2/day. The recommended dose of tegafur for this schedule of administration is 1.0 g/m2/day.
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PMID:Phase I evaluation of oral tegafur. 641 58

The activity and toxicity of UFT (Tegafur and Uracil) in a 4:1 molar concentration, plus leucovorin (LV), were evaluated in the treatment of 45 patients with advanced, bidimensionally measurable metastatic colorectal carcinoma. Initially 350 and later 300 mg/m2/day, plus 150 mg LV, as administered in divided doses every 8 h for 28 days. After two courses of treatment, responses were evaluated. The overall response rate was 42.2%, with responses observed in liver (n = 18), lung (n = 6), and bone (n = 1). Five of the 7 patients who received 350 mg/m2 UFT experienced prolonged grade 3 diarrhea, resulting in a dose reduction to 300 mg/m2; 9 patients in the 300-mg/m2 group experienced grade 3 diarrhea, vomiting, abdominal cramping, and fatigue. Minor toxic effects included oral mucositis and rash. The oral regimen of 300 mg/m2/day UFT, plus 150 mg/day LV, administered for 28 days appears to have significant activity against metastatic colorectal carcinoma. The treatment is well tolerated; neutropenia did not occur, and oral mucositis was not significant, even though both are characteristic of intravenous schedules of 5-fluorouracil plus LV. The results of this trial constitutes the basis of phase III clinical trials comparing this oral schedule with intravenous 5-FU and LV to compare clinical efficacy, impact on well-being, and cost. In addition, the current National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant colon clinical trial (CO-6) will compare this 28-day schedule of UFT plus oral leucovorin with a weekly regimen of intravenous 5-fluorouracil plus leucovorin in the postoperative adjuvant therapy of Dukes' B and C colon cancer patients.
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PMID:Phase II study of UFT plus leucovorin in colorectal cancer. 897 80

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

Continuous 5-fluorouracil (5-FU) infusion during radiation therapy is superior to the application of bolus 5-FU schedules. As an oral therapy, that provides prolonged fluoropyrimidine exposure, uracil and Tegafur (UFT) plus leucovorin (LV) has shown favorable activity with only moderate toxicity in colorectal cancer. The present study was designed to evaluate the safety of UFT+LV combined with pelvic radiation to determine the maximum-tolerated dose (MTD) in recurrent rectal cancer. Patients with recurrent rectal cancer received escalating doses of UFT (starting at 250 mg/m /day with 50 mg/m /day increments between consecutive cohorts) and fixed doses of LV (90 mg). The UFT+LV combination was given 5 days per week simultaneously to a 5-week course of irradiation up to a total dose of 50.4 Gy, 1.8 Gy daily fractions followed by a boost of 5.4 or 9.0 Gy to the gross tumor volume. Nineteen patients were treated and 14 received the full chemotherapy with delivery of all planned radiotherapy. The MTD of UFT was 400 mg/m /day due to the occurrence of dose-limiting diarrhea and emesis. Toxicities were mild and manageable on the lower dose levels. Treatment was feasible mainly on an outpatient base. We conclude that combined chemoradiation with oral UFT+LV is feasible and well tolerated for recurrent rectal cancer patients undergoing pelvic radiation. The safety profile appears comparable to that of i.v. dosing without requiring any i.v. port systems. The recommended doses for further phase II chemoradiation trials are 350 mg/m /day UFT+90 mg LV.
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PMID:Phase I study of oral uracil and Tegafur plus leucovorin and pelvic radiation in patients with recurrent rectal cancer. 1243 34

The early institutional experience in the neoadjuvant treatment of potentially resectable pancreatic carcinoma using oral Tegafur as radioenhancing agent is analyzed. Fifteen patients (10 male and 5 female, mean age of 61 years) were treated over a 30-month period. Tegafur dose was 1,200 mg/d along the external radiotherapy period (45-55 consecutive days). Preoperative radiotherapy achieved a total dose of 45 to 50 Gy (1.8 Gy/d). Intraoperative electron boost (10-15 Gy) was delivered at the time of surgery. Hematologic tolerance showed a significant decrease of neutrophil and platelet counts from the outset to the end of the neoadjuvant period (p = 0.001 and p = 0.004, respectively). Five grade III vomiting episodes (33%) were also registered. In 9 patients (60%), surgical resection was performed after chemoradiation. Three complete pathologic responses (pT0 specimens) were identified; in seven cases, the resection achieved tumor-free surgical margins of the specimen. With a median follow-up of 21 months, median survival time was 17 months, with actuarial rates of 45% at 1 year and 24% at 3 years. Median survival for the resected patients was 23 months, and for the unresected patients median survival was 8 months (p = 0.02). The overall median survival in completely resected patients was 28 months, with a 71% survival rate at 1 and 3 years. It is concluded that the treatment scheme described is feasible and acceptably tolerated. The use of oral Tegafur seems to induce results similar to those of other therapeutic protocols using intravenous radioenhancing chemotherapy.
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PMID:Neoadjuvant chemoradiation with tegafur in cancer of the pancreas: initial analysis of clinical tolerance and outcome. 1528 26

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

To evaluate ambulatory patient cancer chemotherapy, the clinical response, toxicities and survival time were analysed among 19 patients with non-curative or recurrent colorectal cancer who were treated by Uracil/Tegafur (UFT) plus oral Leucovorin (UZEL) for the past 2 years. The patients were administered UFT (300 mg/m2/day) and UZEL (75 mg/body/day) for 28 days with a one-week interval every 35 days as one course.A partial response (PR) was observed in 6 patients (31.6%) and stable disease (SD) in 8. The median survival time was 16 months. Although nausea/vomiting, diarrhea and leucopenia were noted, no severe side effects were observed. These results suggested that UFT plus Leucovorin therapy might be a useful cancer chemotherapy for ambulatory patients with advanced colorectal cancer.
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PMID:[Clinical study of ambulatory patient cancer chemotherapy for advanced colorectal cancer]. 1635 33