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)

Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.
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PMID:Efficacy of low-dose methotrexate in rheumatoid arthritis. 388 72

5-Formyl-tetrahydrofolate [citrovorum factor (CF)] is commonly used for preventing or reversing toxicity due to treatment with high-dose methotrexate (HDMTX). In vivo, CF is converted to 5-methyltetrahydrofolate (MTHF) and then to the 5,10-methylene tetrahydrofolate, which is the active coenzyme involved in thymidine synthesis. In this study, MTHF was used for protection from toxicity following larger doses of MTX than previously studied, doses which could not be tolerated without effective "rescue." Fifteen patients were given 18 courses of MTX in escalating doses (1-24 g) followed by MTHF. The toxic effects observed included: leukopenia, thrombocytopenia, mucositis, nausea, vomiting, and elevation of serum creatinine and serum transaminase. The side effects were reversible and all patients recovered fully. "Matched pairs" comparison of CF and MTHF rescue in five patients showed no difference in rescue efficacy between the two agents. Since ten of the treatments consisted of 12 and 24 g of MTX, doses potentially fatal without rescue, MTHF is an effective agent for prevention of MTX toxicity.
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PMID:Rescue from high-dose methotrexate with 5-methyltetrahydrofolate. 394 89

The effects of combination chemotherapy including mitoxantrone (MXN) "M-VEMFH" for advanced breast cancer were studied. The M-VEMFH regimen consisted of MXN 7 mg/m2, VCR 0.7 mg/m2, EX 333 mg/m2, MTX 13.3 mg/m2 i.v. on day 1, 5-FU 333 mg/m2 i.v. from day 1 to day 5 and pred. (H) 60 mg/m2 p.o. with tapering off in 2 weeks. In 7 cases heavily pretreated with combination chemotherapy including ADR, CR 2, PR 2, NC 2 and PD 1 were observed (response rate 57.1%). In 5 cases without prior ADR, PR 1, NC 2 and PD 2 were obtained. One case given 586 mg/m2 of prior ADR died of congestive heart failure after administration of 47 mg/m2 of NXN. One case died of sepsis. The other side effects were stomatitis, vulvitis, abnormal gustation, nausea, vomiting and alopecia. M-VEMFH is effective combination chemotherapy for advanced breast cancer resistant to ADR, but care must be exerted due to the accompanying cardiotoxicity and leukopenia.
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PMID:[Effects of combination chemotherapy M-VEMFH including mitoxantrone in advanced breast cancer]. 405 16

Twenty-six patients with advanced squamous cell cancer of the head and neck were treated with bleomycin, Oncovin, mitomycin C, and methotrexate (BOMM) for ten weeks. Partial and nonresponders then received adriamycin, cisplatin, and cyclophosphamide (APC) in a planned sequential program. The response rate to BOMM was 65% (19% complete remission, CR). The overall response rate to APC was 20%. Only three of eight nonresponders to BOMM could receive APC and non responded. Six of seven partial responders received APC and only one responded. One complete responder to BOMM received APC at relapse and attained a partial response. The major side effects of BOMM were mucositis and myelosuppression. Patients receiving methotrexate 60-72 hours following the bleomycin infusion had less myelosuppression than patients who were treated 36-42 hours after bleomycin. The toxicities with APC included nausea, vomiting, and myelosuppression. Including a prior series, a total of 45 patients have been treated with BOMM with a 71% response rate (69% in previously irradiated patients). Twenty-eight percent of previously treated patients achieved complete remission, and two of these patients are disease free at 31 and 37 months. Methotrexate dose-rate alteration to low dose twice weekly followed by a single dose of oral leucovorin did not improve the complete or partial response rate when compared to weekly methotrexate administration. The complete remission rate and response duration were also not improved by the planned sequential use of this cisplatin-containing regimen.
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PMID:Intensive sequential chemotherapy with bleomycin, Oncovin, mitomycin C, and methotrexate followed by adriamycin, cisplatin, and cyclosphosphamide in squamous cell cancer of the head and neck. 618 32

23 patients with osteogenic sarcoma were observed during 142 6-hour high-dose infusions of methotrexate (MTX, 3,000--8,200 mg/m2). Calcium leukovorin was given by intravenous injection at 3-hour intervals beginning 2 h after the completion of each MTX infusion with extension of the intervals to 6 h following the first day of rescue. All patients also received continuous intravenous infusions of alkalinized fluids for the entire duration of leukovorin rescue. No larger doses of leukovorin were given to any patient. Three of the 142 MTX infusions resulted in mild cytotoxic side effects. Plasma MTX clearance ranged from 90 to 600 ml/min among the 62 infusions where plasma clearance could be accurately calculated. The 3 patients with mild toxicity had low drug clearance, but others with similar low MTX clearance experienced no apparent toxic effects beyond the expected transient nausea.
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PMID:High-dose methotrexate with a safe rescue program. 697 32

A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.
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PMID:Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. 753 17

Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5-hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a 1-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline.
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PMID:Aminophylline for methotrexate-induced neurotoxicity. 777 73

The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.
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PMID:Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma. 792 45

A case report of toxicity following concurrent administration of high-dose methotrexate and amoxycillin is presented. A 16-year-old male patient was administered 10 high-dose methotrexate cycles for treatment of a fully malignant osteogenic sarcoma. Methotrexate was administered at a dosage of 8 g/m2 and infused intravenously over a 6-h period. The patient received pre- and posttreatment hydration and sodium bicarbonate for alkalinization of urine. Calcium folinate rescue was performed when appropriate. During the 10th cycle, coadministration of amoxycillin (1 g/6 h, p.o.) resulted in prolonged and marked enhancement of methotrexate serum levels. Pharmacokinetic parameters obtained in cycle 10 indicate significant differences for total plasma clearance, mean residence time, and distribution half-life when compared to those in cycles 1-9. Amoxycillin decreased the renal clearance of methotrexate, probably by competition at the common tubular secretion system and by secondary methotrexate-induced renal impairment. The patient experienced acute and subacute toxicity with renal failure, myelosuppression, mucositis, nausea, vomiting, fever, and dermatologic abnormalities. Patients receiving amoxycillin during methotrexate therapy should be closely monitored to avoid severe toxicity.
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PMID:Pharmacokinetic interaction between high-dose methotrexate and amoxycillin. 824 43

The role and adverse effects of methotrexate in the treatment of chronic corticosteroid-dependent asthma are discussed. Methotrexate is a folic acid antagonist that has been used as an anti-inflammatory agent in the treatment of arthritis. It also appears to be effective in reducing the corticosteroid requirements in patients with chronic corticosteroid-dependent asthma, a use that was first reported in 1986. Studies of this use of methotrexate in adults support a trial of methotrexate in patients with severe asthma who have been unable to discontinue corticosteroid use despite aggressive management of their asthma and who are experiencing severe corticosteroid toxicity. Experience with methotrexate in children with asthma is limited to case series. Adverse effects associated with the use of methotrexate for treatment of corticosteroid-dependent asthma include nausea, elevated serum aminotransferase, diarrhea, and thinning of hair. While methotrexate appears to reduce corticosteroid requirements in patients with chronic corticosteroid-dependent asthma, its role in asthma therapy still needs to be clarified.
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PMID:Methotrexate for the treatment of chronic corticosteroid-dependent asthma. 825 56


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