Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “methotrexate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources
PubMed1984

Methotrexate systemic clearance influences probability of relapse in children with standard-risk acute lymphocytic leukaemia.

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

Bone Marrow Examination↗
PubMedDate not supplied

[Methotrexate for the treatment of patients with chronic cutaneous sarcoidosis: 4 cases].

INTRODUCTION: Pathogenesis of sarcoidosis remains partially unknown. Cutaneous lesions are frequent (20 to 35% of cases). Their clinical features and follow-up data are highly variable. Numerous treatments have been proposed. The clinical features and follow up data of four patients with chronic cutaneous sarcoidosis treated with methotrexate are reported. CASE REPORT: Mean age of patients (3 female, 1 male) was 40 years old (34-49 years). One patient presented with a lupus pernio, two patients with papules and nodules, and the last with an annular lesion of the face. All patients had been previously treated with topical corticosteroids and/or hydroxychloroquine without any success. Patients were treated with methotrexate at doses ranging from 12.5 mg to 30 mg per week for at least 6 months. Complete remission of cutaneous lesions was observed in 3 of 4 patients after a mean treatment duration of 29 months (16 to 36). Methotrexate side effects were observed in one patient (elevated liver enzymes) leading to methotrexate discontinuation. DISCUSSION: Methotrexate seems to be an effective treatment of cutaneous sarcoidosis. It should be used namely in patients who failed to respond to previous treatments with topical corticosteroids or antimalarial drugs.

Adult↗
PubMed2001

Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

PURPOSE: To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. METHODS: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. MAIN OUTCOME MEASURES: Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. RESULTS: A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. CONCLUSIONS: Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

Adolescent↗
PubMed1992

Low-dose methotrexate therapy for ocular inflammatory disease.

BACKGROUND: Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects. METHODS: Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3). RESULTS: Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate. CONCLUSION: Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease.

Adolescent↗
PubMed2000

Identification by RNA-based arbitrarily primed PCR of the involvement of cytochrome c oxidase in the development of resistance to methotrexate.

RNA-based arbitrarily primed PCR (RAP-PCR) was used to identify sequences in CHO K1 cells that were differentially expressed upon methotrexate incubation during the development of resistance to this drug. Ten different RAP products were isolated, cloned and sequenced. Among these, we identified one sequence that showed 84% identity with the nucleotide sequence of rat cytochrome c oxidase subunit II, and 90% identity with the amino acid sequence of this protein. This RAP fragment was up-regulated in a dose- and time-dependent manner. The overexpression of cytochrome c oxidase subunit II mRNA as a result of methotrexate incubation was corroborated by quantitative RT-PCR and Northern blot analysis. Incubation of cells with sodium azide, a specific cytochrome c oxidase inhibitor, decreased the number of resistant colonies after methotrexate treatment. Thus, overexpression of cytochrome c oxidase is involved in the development of resistance to methotrexate. These results suggest that sodium azide may be used as a modulator in chemotherapy with methotrexate.

Animals↗
PubMed1984

Two patterns of skin ulceration induced by methotrexate in patients with psoriasis.

Two patterns of skin ulceration occurred in patients receiving weekly methotrexate for psoriasis. In type I ulceration, psoriatic plaques became painful and eroded shortly after starting methotrexate (MTX) (median, 10 days). Type II ulcers occurred in clinically uninvolved skin affected by other pathology--stasis dermatitis in two and adjacent to an anal fistula in one and had a variable relationship to the duration of methotrexate treatment. Type I ulcers developed at methotrexate doses between 12.5 and 25 (median, 20) mg/wk and healed rapidly (median, 10 days) after dose reduction or withdrawal. Type II ulcers developed at methotrexate doses of 7.5 to 20 (median, 10) mg/wk and took a median of 9 weeks to heal. Type I ulceration may be confused with an exacerbation of psoriasis, and the MTX dose mistakenly increased rather than reduced. Type II ulcers can mimic stasis ulcers and may be overlooked as evidence of MTX toxicity.

Adult↗
PubMed1998

Accelerated cutaneous nodulosis during methotrexate therapy in a patient with rheumatoid arthritis.

Rheumatoid nodulosis is characterized by multiple small subcutaneous granulomatous nodules typically located on the elbows in approximately 20% of patients with rheumatoid arthritis. Accelerated rheumatoid nodulosis, especially involving the hands and feet, has recently been reported in patients receiving methotrexate therapy for rheumatoid arthritis. We describe a woman with seropositive, erosive rheumatoid arthritis who, on two occasions, developed nonperiarticular subcutaneous nodules and new heart murmurs during methotrexate therapy, while her arthritis remained under good control. The nodules resolved after methotrexate was discontinued and recurred after methotrexate was reintroduced. They again resolved after methotrexate was stopped and colchicine was added. Her DNA oligotyping was positive for HLA-DRB1*0401, a genetic risk factor associated with accelerated rheumatoid nodulosis. Cutaneous biopsy specimens revealed palisading granulomas and giant cells consistent with rheumatoid nodulosis.

Antirheumatic Agents↗
PubMed1988

Histochemical changes in the composition of mucins in goblet cells during methotrexate-induced mucosal atrophy in rats.

Changes in the composition of mucins in jejunal goblet cells were investigated histochemically after a single intraperitoneal injection of methotrexate in rats (40 mg methotrexate/kg body weight). At 48 h after injection of methotrexate, when mitotic activity in the crypts approximates to zero, an almost complete disappearance of mucin-containing goblet cells can be observed. At 96h, when proliferative activity in crypts is excessive, neutral mucin- and sialomucin-containing goblet cells dominate in the crypts, whereas in controls the crypts display sulphomucin-containing goblet cells. At 144h neutral mucin- and sulphomucin-containing goblet cells dominate in the crypts. Both at 48 and 96h after injection of methotrexate a significant decrease in the number of villous goblet cells takes place, whereas with respect to the quality of the mucins in the goblet cells no difference can be found in comparison with control rats. At 144h the villi have recovered from the preceding temporary decrease of goblet cells. The histochemical composition of the population of goblet cells is still aberrant and shows goblet cells containing neutral mucins and sulphomucins principally, whereas in controls sialomucin-containing goblet cells dominate on the villi. The established changes in the composition of mucins in goblet cells cannot be attributed to methotrexate-induced malnutrition, as pair-fed control rats clearly demonstrate. Our results clearly demonstrate that conspicuous quantitative as well as qualitative changes in the synthesis of mucins in goblet cells occur during the hyporegenerative and hyperregenerative phase of methotrexate-induced mucosal atrophy.

Animals↗
PubMed1997

The use of folates concomitantly with low-dose pulse methotrexate.

Toxicities related to low-dose weekly methotrexate are largely due to its antifolate properties. Preexisting folate deficiency is associated with methotrexate toxicity in some patients. At the onset of methotrexate therapy and throughout therapy, the physician should be vigilant regarding one or more nutrient deficiencies. A multivitamin and, where appropriate, specific daily folic acid supplements should be employed. The only regimen known presently (through controlled trials) to treat side effects is the low-dose folinic acid (leucovorin) protocol outlined herein. Folic acid may be helpful to treat mild gastrointestinal symptoms. Folinic acid supplementation should be considered prophylactically in those requiring methotrexate who are at increased risk of hepatic disease. Other possible factors besides methotrexate should always be considered with the onset of new patient complaints or laboratory abnormalities. Claims that folic acid therapy is safer and more convenient than folinic acid seem unwarranted when one reviews the literature carefully. Cost differences between folic acid supplementation and folinic acid supplementation have been exaggerated.

Antidotes↗
PubMed2001

[Methotrexate-ciprofloxacin interaction: report of two cases of severe intoxication].

UNLABELLED: Methotrexate elimination may be delayed by different drugs. Such a delay may produce severe toxic complications. CASE REPORTS: We report two cases of adolescents treated for malignant diseases who presented a delayed methotrexate elimination even though they received ciprofloxacin. The first patient had already received several courses of methotrexate without toxicity before this episode. The second patient tolerated methotrexate when ciprofloxacin was not associated to the treatment. CONCLUSION: High-dose methotrexate-ciprofloxacin association should be avoided.

Adolescent↗
PubMed1991

Evidence for two interconverting protein isomers in the methotrexate complex of dihydrofolate reductase from Escherichia coli.

Two-dimensional 1H NMR methods and a knowledge of the X-ray crystal structure have been used to make resonance assignments for the amino acid side chains of dihydrofolate reductase from Escherichia coli complexed with methotrexate. The H7 proton on the pteridine ring of methotrexate was found to have NOEs to the methyl protons of Leu-28 which were assigned by using the L28F mutant. These NOEs indicated that the orientation of the methotrexate pteridine ring is similar in both solution and crystal structures. During the initial assignment process, it became evident that many of the resonances in this complex, unlike those of the folate complex, are severely broadened or doubled. The observation of two distinct sets of resonances in a ratio of approximately 2:1 was attributed to the presence of two protein isomers. At 303 K, NOESY spectra with mixing times of 100 ms did not show interconversion between these isomers. However, exchange cross-peaks were observed in a 700-ms NOESY spectrum at 323 K which demonstrated that these isomers are interconverting slowly on the NMR time scale. Many of the side chains with clearly doubled resonances were located in the beta-sheet and the active site. Preliminary studies on the apoprotein also revealed doubled resonances in the absence of the inhibitor, indicating the existence of the protein isomers prior to methotrexate binding. In contrast to the methotrexate complex, the binary complex with folate and the ternary MTX-NADPH-DHFR complex presented a single enzyme form. These results are proposed to reflect the ability of folate and NADPH to bind predominantly to one protein isomer.

Escherichia coli↗
PubMed1987

Structural comparisons of complexes of methotrexate analogues with Lactobacillus casei dihydrofolate reductase by two-dimensional 1H NMR at 500 MHz.

We have used two-dimensional (2D) NMR methods to examine complexes of Lactobacillus casei dihydrofolate reductase and methotrexate (MTX) analogues having structural modifications of the benzoyl ring [the 3',5'-difluoro and 3',5'-dichloro analogues (II and III)] and also the glutamic acid moiety [the alpha- and gamma-monoamides (IV and V)]. Assignments of the 1H signals in the spectra of the various complexes were made by comparison of their 2D spectra with those of complexes containing methotrexate where we have previously assigned resonances from 32 of the 162 amino acid residues. In the complexes formed with the dihalomethotrexate analogues, the glutamic acid and pteridine ring moieties were shown to bind to the enzyme in a manner similar to that found in the methotrexate-enzyme complex. Perturbations in 1H chemical shifts of protons in Phe-49, Leu-54, and Leu-27 and the methotrexate H7 and NMe protons were observed in the different complexes and were accounted for by changes in orientation of the benzoyl ring in the various complexes (15 degrees and 25 degrees in the difluoro- and dichloromethotrexate complexes, respectively). Binding of oxidized or reduced coenzyme (NADP+ or NADPH) to the binary complexes did not result in different shifts for Leu-27, Leu-54, or Leu-19 protons, and thus, the orientation of the benzoyl ring of the methotrexate analogues is not perturbed greatly by the presence of either oxidized or reduced coenzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Folic Acid Antagonists↗
PubMed2001

Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer.

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725 mg/m2 per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.

Adult↗
PubMed1976

The effect of methotrexate on spontaneous mammary adenocarcinomata in female C3H mice.

The effect of methotrexate on solid rodent tumours has been investigated using the spontaneous mammary adenocarcinoma of the female C3H/Bts mouse. As these tumours exhibit a wide range of volume doubling times, calculations of tumour response to methotrexate must be related to doubling time. When methotrexate is injected into the tumour a dose-dependent tumour response is obtained. Systemic citrovorum "rescue" prevents methotrexate lethalities but reduces tumour response by a factor of 2. Methotrexate-treated tumours have an increased volume doubling time post treatment.

Adenocarcinoma↗
PubMed1990

A phase III randomised trial of cistplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group.

We describe a phase III trial on 200 patients with end stage squamous cell carcinoma of the head and neck. The patients were randomised to one of four treatment arms: cisplatinum alone, methotrexate alone, cisplatinum + 5-FU and cisplatinum + methotrexate. There was no significant difference in the response rates, but the survival of the cisplatinum arm was significantly better than that of the methotrexate arm. The survival of patients receiving cisplatinum as a single agent was longer than that of patients receiving cisplatinum in combination with methotrexate or 5-FU, but not significantly so. Nausea/vomiting and anaemia were significantly more common in the cisplatinum arms than in the methotrexate arm, but the toxicity of combination regimens was not significantly greater than that of cisplatinum used as a single agent.

Aged↗
PubMed1991

Comparative effect of 6S, 6R and 6RS leucovorin on methotrexate rescue and on modulation of 5-fluorouracil.

The comparative efficacy of the pure diastereoisomers of leucovorin, the natural (6S) and the unnatural (6R) forms was compared to the racemic form (6RS). A protective effect in methotrexate-treated CCRF-CEM cells was obtained with 6S at concentrations 100-fold higher than those of methotrexate and with 6RS at concentrations 2-fold greater than those of 6S; however, at low concentrations of methotrexate, 6S was more effective than 6RS in preventing the cytotoxicity of methotrexate; on the opposite, 6R exhibited a protective effect at concentrations 10(4) higher than those of methotrexate. On the same cell line, 6S was shown to enhance the cytotoxic effect of 5 Fluorouracil exactly as 6RS while 6R did not exhibit any enhancing effect on cells exposed to 5 Fluorouracil.

Analysis of Variance↗
PubMed1991

Homocysteine levels in patients with rheumatoid arthritis treated with low-dose methotrexate.

Plasma homocysteine levels were determined in patients who participated in a randomized, double-blind placebo-controlled trial of folate supplementation (1 mg/day) during methotrexate therapy for rheumatoid arthritis. Plasma and red blood cell folate levels before methotrexate therapy were significantly negatively correlated with homocysteine levels. Homocysteine levels were not significantly correlated with the initial C1 index (an assay that measures the folate status of blood mononuclear cells) or the C1 index during methotrexate therapy. There was no significant difference in homocysteine levels between pretreatment and levels drawn at 3 or 6 months. Initial homocysteine levels were predictive of toxicities, such as gastrointestinal intolerance and elevations of liver enzymes in the placebo group. There was no significant correlation between occurrence of toxicity and initial homocysteine levels in the folic acid-supplemented group. Homocysteine levels were not predictive of the efficacy of methotrexate therapy. We conclude that plasma homocysteine levels are correlated with plasma and red blood cell folate levels before methotrexate therapy but is not correlated with folate status in blood mononuclear cells.

Arthritis, Rheumatoid↗
PubMed2003

Low-risk persistent gestational trophoblastic disease treated with low-dose methotrexate: efficacy, acute and long-term effects.

The aim of this study was to evaluate the efficacy and toxicity of low-dose methotrexate with folinic acid rescue in a large series of consecutively treated patients with low-risk persistent gestational trophoblastic disease. Between January 1987 and December 2000, 250 patients were treated with intramuscular methotrexate (50 mg on alternate days 1, 3, 5, 7) with folinic acid (7.5 mg orally on alternate days 2, 4, 6, 8) rescue. The overall complete response rate without recurrence was 72% for first-line treatment and 95% for those who required second-line chemotherapy. Eight women (3.2%) had recurrence following remission and two (0.8%) had new moles. Two women (0.8%) died of their disease giving an overall cure of 99%. Only 10 women (4%) experienced grade III/IV toxicity during the first course of treatment and 13 women (5.2%) subsequently. Toxicity included mucositis and stomatitis, pleuritic chest pain, thrombocytopenia, uterine bleeding, abdominal pain, liver function changes, rash and pericardial effusion. A total of 59 women (23.6%) required second-line chemotherapy; 48 women had methotrexate resistance, eight had methotrexate toxicity and an empirical decision to change therapy was made in three. In all, 11 women (4.4%) had a hysterectomy before, during or after treatment; 141 women (56.4%) became pregnant following treatment: in 128 (90.7%), the outcome was successful. Methotrexate with folinic acid rescue is an effective treatment for low-risk persistent trophoblastic disease. It has minimal severe toxicity, excellent cure rates and does not appear to affect fertility.

Adolescent↗