Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase 2 study of 5'-DFUR in bladder and prostatic cancer was conducted at 15 collaborative institutions including Okayama University. 5'-DFUR was orally administered to patients at a daily dose of 800-1200 mg for more than 4 weeks. Forty-one patients with bladder cancer and 12 patients with prostatic cancer were evaluated. The response rate for bladder cancer was 31.7% (CR, 1 case: PR, 12 cases), against no response with prostatic cancer. Moreover, the concentration of 5-FU in bladder tumors was confirmed to be high. Adverse reactions such as diarrhea, anorexia, and nausea were observed. Thus, 5'-DFUR seems to be useful for the treatment of bladder cancer.
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PMID:[Phase II study of 5'-DFUR treatment of the bladder and prostatic cancer]. 183 24

Ten patients with non-resectable gastric cancer were subjected to a neo-adjuvant chemotherapy (FLEP therapy), consisting of 4 drugs (leucovorin and 5-FU i.v., CDDP and etoposide i.a.) combination therapy from August 1989 to April 1991. The response rate of this therapy with primary lesions, metastatic lymph-nodes (mainly paraaortic lymph nodes), metastatic liver tumor and peritoneal dissemination were 50, 50, 25 and 33%, respectively. Five cases underwent total gastrectomy. Pathological evaluation of these cases was Grade 1 or 2. Side effects were mainly gastrointestinal disturbances, namely stomatitis, nausea, vomiting and anorexia, along with bone marrow suppression. Performance status of these patients improved to a significant degree by the therapy. This therapy seemed to be effective in controlling paraaortic lymph-node metastasis. The advantage of i.a. delivery was investigated by Tc-MAA scintigraphy. The distribution of Tc-MAA after i.a. injection suggested that i.a. chemotherapy enhanced intraabdominal drug concentration. There is no established treatment for far advanced cases, so this therapy seems to be worth a try.
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PMID:[Evaluation of effective neo-adjuvant chemotherapy (FLEP therapy) in the treatment of advanced gastric cancer]. 187 15

Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S)-leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R)-leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower.
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PMID:Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group. 189 77

Between September 1988 and August 1990, we treated 35 women with metastatic breast cancer with a novel regimen containing mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin. This regimen was designed to take full advantage of the favorable toxicity profiles of these agents while maintaining a high level of activity. All patients had received previous chemotherapy (adjuvant only, 15 patients; at least one metastatic regimen, 20 patients). Seven patients had received previous doxorubicin, but none within 6 months of study entry. Of 31 assessable patients, 20 (65%) had objective responses (two complete, 18 partial), with a median response duration of 6 months (range, 3 to 16+ months). Four patients with bone metastases (abnormal bone scan only) and pain were not considered assessable by strict response criteria; two of these patients had sustained symptomatic relief for 6 and 8 months, respectively. Myelosuppression was the most frequent toxicity but was mild in most patients; only four hospitalizations for fever and neutropenia were required (2% of courses). No severe thrombocytopenia occurred and no RBC transfusions were required. Alopecia, mucositis, and nausea/vomiting were uncommon and were not severe in any patient. The combination of mitoxantrone, 5-FU, and high-dose leucovorin is well tolerated and active as a first- or second-line treatment for metastatic breast cancer. Comparison with other standard regimens for breast cancer is indicated.
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PMID:Mitoxantrone, fluorouracil, and high-dose leucovorin: an effective, well-tolerated regimen for metastatic breast cancer. 191 22

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

Continuous hepatic arterial infusion chemotherapy using implantable reservoir was performed for liver metastases from colorectal cancer, and the therapeutic effects, side effects, and complications were evaluated. 9 patients with unresectable liver metastases were as follows, 1. Group A; 3 patients, MMC 2 mg.one shot + 5-FU 250 mg/day.continuous infusion x 14 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 2. Group B; 4 patients, MMC 2 mg.one shot + 5-FU 500 mg/day.continuous infusion x 7 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 3. Group C; 2 patients, 5-FU 500 mg/day.continuous infusion x 14 days, and then free from agents for 14 days. In 2 of 3 group A patients, the catheters became dislocated and one died of perforation of duodenum. In group A and group B, no severe side effects were noted. But both of group C patients showed nausea, vomiting and diarrhea. In 8 of 9 patients (89%), serum CEA level fell below the preoperative level. In 4 of 7 patients who underwent CT scan, the size of the tumor regressed. Total infused dose of 5-FU was 8.17 +/- 7.56 g in group A, 16.9 +/- 2.88 g in group B, and 21.0 +/- 9.90 g in group C on average. In 2 patients of group B, therapy was repeated seven times.
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PMID:[Continuous hepatic arterial infusion chemotherapy using implantable reservoir in liver metastases from colorectal cancer]. 211 7

5-Fluorouracil (5-FU) has been the treatment of choice for colorectal carcinoma with an overall response rate of about 20%. Recent studies have shown that folate (LV) can increase 5-FU therapeutic efficacy, achieving about a 40% response rate without a clear impact on survival. Cisplatinum (CDDP) is usually inactive in colorectal carcinoma, but the association with 5-FU results in a synergistic antineoplastic effect. A phase I-II study was done to assess the maximally tolerated dose (MTD) of CDDP in association with 5-FU + LV. The MTD for CDDP was 20 mg/m2/wk in association with 5-FU 400-500 mg/m2/wk and LV 500 mg/m2/wk. WHO criteria were used for evaluation of both toxicity and response. In the phase I part we found that the main side-effect in 27 evaluable patients (pts) was gastrointestinal toxicity, mainly in the form of nausea/vomiting (92%) and diarrhea (70%) which caused one therapy-related death. Renal (26%) and marrow (59%) toxicity were acceptable. In the phase II part of the study 1 out of 19 evaluable pts (5%) had a complete response of 309 days, 3 pts achieved a partial response (16%) with a median duration od 410 days, 2 pts had a minimal response (10%) with a median duration of 261 days, and 8 pts experienced no change (42%) with a mean duration of 196 + days. In our opinion the 21% response rate obtained in this series is not satisfactory. Nevertheless the very high number of minimal response + no change patients together with the interesting impact on survival in responders may suggest further phase II-III studies.
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PMID:A phase I-II study on the toxicity and therapeutic efficacy of 5-fluorouracil in combination with leucovorin and cisplatinum in patients with advanced colorectal carcinoma. 219 35

Thirteen patients with previously untreated advanced squamous cell carcinoma of the esophagus were treated with pre-radiation chemotherapy followed by radiation therapy. The chemotherapy consisted of two or three cycles of Cisplatin and 120 hour continuous infusion of 5-Fluorouracil. Three patients showed complete response (CR), three partial response (PR), three minor response (MR) and four non-response (NR). The overall response rate was 46%. The predominant side effects were nausea, vomiting and anorexia. Mild or moderate degree of anemia and leukocytopenia were also noticed. However, no serious toxicity was observed. Radiation therapy was administered to eleven of the thirteen patients, excluding one patient who refused it and one patient who died during chemotherapy. In two of the eleven cases, however, radiotherapy was discontinued because of MR, and surgery was performed. In one additional case, post-radiotherapy surgery was performed. One of these three cases received curative esophagectomy. After definitive treatment, CR was obtained in 54% (7 of 13), PR in 15% (2 of 13), MR in 15% and NR in 15%. The non-effective patients (PR + MR + NR) died within nine months after the initiation of treatment. Two of the CR patients later died, one due to local recurrence and another due to aortic-esophageal fistula with no residual cancer discovered at autopsy. The remaining CR patients are still alive and well, after 11.5 to 32 months. Although the follow-up period is yet short, the combination of radiation therapy with pre-radiotherapy chemotherapy appears to be an effective treatment.
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PMID:[Combined radiotherapy and pre-radiation chemotherapy with cisplatin and 5-fluorouracil for advanced esophageal carcinoma. II. Clinical evaluation in cases with higher than T2 stage]. 223 Apr 44

Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid.
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PMID:Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. 223 Aug 97

A patient with FIGO stage IIIb adenocarcinoma of the uterine cervix (moderately differentiated, endocervical type) underwent an exploratory laparotomy because of a direct cancer invasion to the bladder wall, and then she was treated with consecutive intraarterial (IA) CDDP (10 mg/day) combined with continuous IA 5-FU (250 mg/day). Six weeks after, CR (complete response) was obtained by this IA chemotherapy (total dose; 5-FU: 10,500 mg, CDDP: 300 mg). Further 5-weeks-IA chemotherapy was added to keep the "CR" effect (final total dose; 5-FU: 19,250 mg, CDDP: 500 mg). The only toxic sign was a mild nausea. The patient's PS (performance status) was 0 (normal activity) and thereafter she could undergo a "curative" radical hysterectomy. The cancer invasion to the bladder wall observed at the first exploratory surgery completely disappeared histologically as well as macroscopically. In obtained material, small "viable" cancer focus was found in the cervical canal but the margin was free, and all nodes were negative. Postoperatively, the patient has receiving a continuous IA 5-FU (125 mg/day) for 13 months as a maintenance and she is free of disease (NED) with a normal activity (PS = 0). The present treatment modality is considered to be promising for advanced cervical adenocarcinoma having a poor prognosis due to its low sensitivity to radiotherapy.
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PMID:[Effective continuous intraarterial chemotherapy for a patient with FIGO stage IIIb cervical adenocarcinoma invasing the bladder wall]. 226 37


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