Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 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

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.
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PMID:Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). 241 66

One hundred and ninety-one cases of acute lymphoblastic leukaemia were entered in a trial in which, for five months, all received cytotoxic therapy with prednisolone, vincristine, mercaptopurine, L-asparaginase, and methotrexate (the latter in high dosage followed by folinic acid). Patients were then randomized to receive immunotherapy (B.C.G.), twice-weekly methotrexate, or no further treatment.One hundred and seventy-seven patients (93%) achieved full remission and at the time of analysis, 26 months from the beginning of the trial, 143 were still alive, including 70 in their first remission. Median "post-intensive" remission lengths were 17 weeks (no treatment), 27 weeks (B.C.G.), and 52 weeks (methotrexate). The prolongation of remission by methotrexate was most evident in those patients with low initial white cell counts. B.C.G. seemed to cause lymphocytosis but was without other conspicuous effect. The incidence of toxic reactions is reported, including an unusually low rate of anaphylaxis with L-asparaginase.These preliminary results are discussed and compared with those of similar trials.
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PMID:Treatment of acute lymphoblastic leukaemia. Comparison of immunotherapy (B.C.G.), intermittent methotrexate, and no therapy after a five-month intensive cytotoxic regimen ((Concord trial). Preliminary report to the Medical Research Council by the Leukaemia Committee and the Working Party on Leukaemia in Childhood. 494 Jan 57

The recommendations for the practical stability of anticancer drugs published in 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparaginase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, temsirolimus).
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PMID:SFPO and ESOP recommendations for the practical stability of anticancer drugs: an update. 2420 90