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)

"BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. The authors attempted to irradiate 3-5 days after the BUdR and antimetabolite had been infused via the superficial temporal artery, in 12 malignant oral tumours (11 squamous cell carcinomas and 1 reticulum-cell sarcoma). BUdR 50-250 mg/day, antimetabolites (5-FU) 10-250 mg/day and a total irradiation dose of 6000 rads by 6 MeV Linac X-ray or Co-60 gamma ray, 200 rads/day were given. 9 marked responses, 2 moderate responses and 1 no response (2 cases were operated on by local resection) were obtained by the authors. Side effects of treatment were observed during the course of "BAR" therapy. Stomatitis was found in all patients and it occurred on the mucosa of the tumour-affected site especially. Dermatitis of the skin of the face was noted in 6 cases, resembling irradiation dermatitis. Fever was observed in 4 cases and it always occurred after irradiation. Diarrhoea was noted in 3 cases and occurred before irradiation, 2 out of 3 were given BUdR 0.1 g and the remaining one was given BUdR 1 g, and 5-FU lg. In addition, there were: 1 loss of appetite, 1 nausea and 1 exfoliation of nails.
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PMID:The effects of "BAR" therapy on oral malignant tumors. 35 11

In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5-FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m2/day continuous infusion IV days 1-5, followed by weekly IV infusions of 5-FU 750 mg/m2 beginning on day 12. Patients concurrently received IFN alpha-2a 9 x 10(6) IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38-80) with a median Karnofsky performance status of 90 (range 60-100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5-6 months) and the median survival was 5 months (range 2-14.5 + months).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma. A Hoosier Oncology Group study. 142 32

From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer.
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PMID:[Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. 146 46

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) daily for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridine, a new fluoropyrimidine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64%), lung (35%), local recurrence (10%) and peritoneum (10%). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxifluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.
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PMID:Reversal of resistance to doxifluridine and fluorouracil in metastatic colorectal cancer: the role of high-dose folinic acid. 146 82

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

Based on promising results with 5-FU/FA or 5-FU/IFN-alpha in colorectal cancer, a pilot study was initiated to evaluate the effects of the combination 5-FU/FA/interferon alfa (IFN-alpha) in patients with advanced pancreatic cancer. Patients received 9 million units (MU) IFN-alpha subcutaneously three times a week or 6 MU IFN-alpha once a week; 500 mg/m2 5-FU via an intravenous bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of FA, once a week. Fourteen patients, all previously untreated with chemotherapy, were enrolled; 13 (two females/11 males) were evaluable for response and toxicity (one too early). The median performance status was 80% (range, 60 to 100) and the median age 62 years. Besides the inoperable primary tumor, metastatic sites were liver, lung, and peritoneum. Three of 13 patients had a partial remission, three of 13 patients a minor response, and four of 13 patients no change. Three patients had progressive disease. Until now, no complete remission was seen. Median duration of response was 4+ months; median survival has not been reached yet. Of all patients there were three instances of World Health Organization grade 3 toxicity: fatigue (one of 13), nausea (one of 13), and diarrhea (one of 13); grade 4 toxicity did not occur. Although overall toxicity was moderate, most patients experienced a reduction of well-being. Therefore in all patients the dose of IFN was reduced (from 3 x 9 MU/week to 1 x 6 MU/week). Our preliminary data suggest that biochemical modulation of 5-FU with FA and IFN-alpha (reduced dosage) is effective in pancreatic cancer with moderate toxicity, warranting further study.
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PMID:Combination fluorouracil, folinic acid, and interferon alfa-2a: an active regimen in advanced pancreatic carcinoma. 155 50

60 patients with advanced carcinomas of the oropharynx and hypopharynx underwent chemotherapy, either with 5-FU/Cisplatin (n = 30) or with 5-FU/Carboplatin (n = 30). The remission-rates (complete and partial remissions) were comparable in both groups. The rate of complete remissions, however, was statistically significant higher in the cisplatinum group (6 patients) than in the carboplatinum group (1 patient). 2 patients of the 5-FU/Cis-group and 4 patients of the 5-FU/Carbo-group developed a progressive disease during chemotherapy. Statistically significant differences were found in the nephrotoxic and myelotoxic side effects between both therapy groups: nephrotoxic side effects were more frequent in the 5-FU/Cis-group, whereas myelotoxic side effects occurred mainly in the 5-FU/Carbo-group. The chemotherapy with 5-FU/Carboplatin was better tolerated by the patients than in the 5-FU/Cisplatinum-group. In the 5-FU/Carbo-group especially a lower rate and severity of loss in weight, nausea, vomiting, alopecia and mucositis/stomatitis was observed. No statistically significant differences were found in ototoxic side effects between both groups.
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PMID:[Antineoplastic effectiveness and unwanted side effects of polychemotherapy of extensive oro- and hypopharyngeal cancers--results of a prospective therapy study with 5-FU/cisplatin versus 5-FU/carboplatin]. 161 47

The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy and to better comparability of future studies.
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PMID:New developments in the treatment of gastric carcinoma. 168 67

Preclinical and clinical studies demonstrate that the selective antitumor activity of fluorouracil (5-FU) is enhanced by agents which perturb certain intracellular nucleotide pools. We previously demonstrated that the combination of N-phosphonacetyl-L-aspartate (PALA), which depletes pyrimidine nucleotide pools, and 5-FU yielded a 43% response rate among 37 assessable patients with colorectal carcinoma. In preclinical tumor models, 6-methylmercaptopurine riboside (MMPR), an inhibitor of purine synthesis, elevates phosphoribosylpyrophosphate (PRPP) pools and promotes the anabolism of 5-FU to fluorinated nucleotides. In vivo, the addition of MMPR enhances the therapeutic efficacy of PALA-5-FU. In a phase I trial, we sought to determine the optimal dose and schedule of MMPR in combination with PALA (250 mg/m2 on day 1) and 5-FU (1300 mg/m2 by 24-hour infusion on day 2). MMPR (75-225 mg/m2) was given intravenously on day 1 to 27 patients with solid tumors (15 colorectal, seven breast, five other). Toxic effects were mild to moderate and included leukopenia, mucositis, nausea, or rash. Two of seven patients given MMPR at 225 mg/m2 had grade 3 diarrhea. PRPP was measured using a [14C]orotic acid 14CO2 release assay in tumor biopsy specimens obtained before and 12 hours and 24 hours after MMPR doses were given to 20 patients. The addition of MMPR elevated PRPP pools in human solid tumors. At 12 hours after treatment, two (50%) of four patients showed a twofold or greater elevation of PRPP at the MMPR dose level of 75 mg/m2; a similar elevation was observed in five (71%) of seven patients given 150 mg/m2 MMPR and in three (43%) of seven patients given 225 mg/m2 MMPR. At 24 hours after treatment, results for the respective dose levels of MMPR were two (33%) of six patients, one (20%) of five patients, and four (57%) of seven patients. Administration of the two highest MMPR dose levels appeared to result in a greater increase in tumor PRPP levels. However, toxicity was greater at the 225 mg/m2 dose level; therefore, the 150 mg/m2 dose level was favored. Tumor levels of PRPP decreased between 12 hours and 24 hours in nine (56%) of 16 patients. This time course indicates that MMPR should be administered at the beginning of the 24-hour infusion of 5-FU.
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PMID:Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine riboside: optimization of 6-methylmercaptopurine riboside dose and schedule through biochemical analysis of sequential tumor biopsy specimens. 171 7

Neo-adjuvant chemotherapy with CDDP combination was introduced into the treatment of advanced head and neck cancer. Twenty-three patients with s.c.c of head and neck were given combination chemotherapy consisting of CDDP, VDS and 5-FU before surgical treatment in our department. CR and PR of this trial in all patients were 4 and 35%, respectively. The WBC nadir occurred around 2 weeks later, but all the patients recovered prior to the next cycle or surgical treatment. Renal dysfunction, nausea, vomiting and depilation were generally mild. VDS is useful as one of the neo-adjuvant drugs for the treatment of head and neck cancer. Long-term observation in connection with this treatment is required.
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PMID:[Neo-adjuvant chemotherapy with cisplatin, 5-fluorouracil, vindesine in head and neck cancer]. 173 33


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