Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.
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PMID:Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate. 27 87

The combination of sequential L-asparaginase and methotrexate (MTX) was evaluated in 33 patients with advanced refractory breast cancer. There were nine partial responses and one complete response, giving an overall response rate of 30% and a median duration of response of 8 months. Five of 17 patients (28%) who had received prior MTX at doses of less than 50 mg/m2 responded. Toxicity was acceptable. Moderate-to-severe stomatitis occurred in most patients and was the dose-limiting factor. Myelosuppression was minimal until the dose of MTX was escalated to greater than or equal to 180 mg/m2. The maximum tolerated dose of MTX was 280 mg/m2 and the median toxic dose was 220 mg/m2. These data indicate a selective "rescue" from MTX damage to normal target tissue by L-asparaginase. The antitumor effect observed even in patients who had been previously exposed to conventional doses of MTX suggests a possible improved therapeutic index of MTX given sequentially with L-asparaginase in this combination.
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PMID:Phase II study with sequential L-asparaginase and methotrexate in advanced refractory breast cancer. 36 95

Forty-one children with refractory acute nonlymphocytic leukemia (ANLL) were treated from March 1975 to February 1979 with a schedule-dependent combination of methotrexate (MTX) and L-asparaginase. Intravenous (IV) MTX was followed 24 hours later by IV L-asparaginase (10,000 units [U]/m2). The MTX dose was started at 60 to 100 mg/m2 and was escalated by 20 to 40 mg/m2 as tolerated. This sequence was repeated every 7 to 10 days. Eight patients (20%) achieved a complete remission (CR) and six others had a partial response (PR), with clearance of blasts from the peripheral blood and reduction of bone marrow blasts to less than 25% of nucleated marrow cells. Responding patients received a median maximum MTX dose of 120 mg/m2 (range, 60 to 220 mg/m2). The median number of courses required to achieve a CR was 6 (range, 2 to 13 courses). Toxicity consisted of allergic reactions to L-asparaginase (n = 12), stomatitis (n = 6), minimal elevation of hepatic enzymes (n = 2), and hyperglycemia (n = 1). Treatment was given on an outpatient basis in 95% of all courses. The data indicate that this combination therapy has antileukemic activity and is relatively nontoxic in childhood ANLL.
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PMID:Methotrexate plus L-asparaginase. An active combination for children with acute nonlymphocytic leukemia. 234 Apr 62

Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
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PMID:Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia. 693 51

We have treated 37 adults with acute lymphoblastic leukemia (ALL), who have relapsed on previous intensive chemotherapy, with a combination of L-asparaginase and methotrexate (MTX) +/- ifosfamide. The initial study included 26 patients who received the two-drug combination of L-asparaginase and MTX given sequentially. Of the 26 patients, 15 (58%) achieved complete remission (CR), while 3 patients had a partial remission (PR), resulting in an overall response rate of 69%. The median duration of CR was 17.5 weeks. The median survival of complete responders was 39 weeks compared with 10 weeks for failures (P=0.001). The regimen was generally well tolerated and it was possible to give MTX doses of up to 400 mg/m2 with minimal myelosuppression, and severe stomatitis was infrequent. A further study involved the use of this regimen combined with ifosfamide in 11 patients. In this continuing study, there were six CR's (55%) and two PR's, with an overall response rate of 73%. The median duration of CR was 14+ weeks, and the median survival was 40+ weeks. Combination chemotherapy with asparaginase and MTX is effective in inducing remission in adults with ALL in relapse. It should now be considered for inclusion as part of induction therapy of previously untreated adults with ALL.
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PMID:Asparaginase and methotrexate combination chemotherapy in relapsed acute lymphoblastic leukemia in adults. 694 10

Moderate doses of methotrexate and L-asparaginase were added to standard doses fo 5-fluorouracil, Adriamycin, and cyclophosphamide in an attempt to improve the overall response rate and survival following chemotherapy. In addition, nonspecific immunotherapy with either Corynebacterium parvum or Pseudomonas vaccine was integrated into this prospective randomized clinical trial. The overall toxicity (degree of granulocytopenia and thrombocytopenia, length of myelosuppression, and incidence of myelosuppression-related infection and infectious deaths) increased considerably and led to the termination of patient accrual. The incidence of stomatitis and diarrhea was also increased with the addition of methotrexate and L-asparaginase, and apparently was potentiated by the addition of Pseudomonas vaccine to this five-drug combination.
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PMID:Chemoimmunotherapy for metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, methotrexate, L-asparaginase, Corynebacterium parvum, and Pseudomonas vaccine. 699 Nov 3