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)

One hundred thirty-seven children with previously untreated acute lymphoblastic leukemia were entered into a new program that included intermittent combination chemotherapy featuring Adriamycin. Remission induction was initially randomized to vincristine and prednisone with or without an anthracycline. All children received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal methotrexate. There were no primary failures of CNS prophylaxis. Complications were primarily infectious. Clinical evidence of cardiotoxicity and leukoencephalopathy were not observed. The time to enter complete remission and the presence of an anterior mediastinal mass at diagnosis were found to be statistically significant adverse prognostic factors, whereas presenting age and white blood count were not. With a median follow-up of 26 mo, and using life plot analysis, 65% of the children have remianed in continuous complete remission.
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PMID:Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. 27 7

Twenty-one children with acute nonlymphoblastic leukemia (ANLL) were treated with a combination regimen consisting of arabinosyl cytosine (Ara-C), 6-thioguanine (TG), and Adriamycin, The incidence of complete remission was 74%. For consolidation, addition courses of Ara-C and TG were given, followed by L-asparaginase. The maintenance program was the same as that for the lymphoblastic type (L-2) including intrathecal methotrexate for prophylaxis of meningeal leukemia. Of the 16 who were evaluable for the duration of complete remission, six developed bone marrow relapse, one meningeal leukemia within 3-14 months after entering complete remission and one was lost to follow-up. Eight remain in complete remission for 9-72 months. In five of eight, chemotherapy has been terminated after 3 years, and all continue in remission for 11-32 months post-treatment. Although the results do not compare well to those of the lymphoblastic morphology, long-term disease-free survival can be achieved with multiple-drug intensive treatment in childhood ANLL.
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PMID:Treatment of acute nonlymphoblastic leukemia in children with a multiple-drug protocol. 90 61

A number of therapeutic agents including L-asparaginase, Actinomycin-D, CCNU, Hydroxyurea, 5-FU, Cis-platinum, Cyclophosphamide, orchiectomy, Adriamycin and DES alone and in various combinations has been applied against the Dunning R-3327 rat prostatic adenocarcinoma subline G. We have found a parallel between the results of this study and those of similar therapeutic application to the human tumor. We conclude that this animal model may prove to be a useful screening system for agents against human prostatic cancer.
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PMID:Chemotherapy of the transplantable adenocarcinoma (R-3327) of the Copenhagen rat. 91 40

From 1985 to 1989, we treated a total of 24 adult patients with acute lymphoblastic leukemia, 17 males and 7 females, median age 26 (range 16-70 yr), with a protocol consisting of remission induction with Adriamycin (ADR), vincristine (VCR), prednisolone (PDN) and 1-asparaginase (ASP), followed by two consolidation courses with ADR, VCR, cyclophosphamide, methotrexate and PDN (Ad-VEMP), combined with CNS-prophylaxis (intrathecal MTX and PDN). Cyclic chemotherapy with VMM (vindesine, 6-MP and MTX) and Ad-VEMP regimen or therapy with VMM regimen only was used to maintain remission. Twenty patients (83.3%) achieved complete remission. The median durations of overall survival and complete remission were 20 and 18 months respectively. The significant unfavorable prognostic factors associated with survival were old age (more than 50 yr), high WBC counts on admission (more than 20,000/microliters) and low nadir of WBC counts (less than 500/microliters). The responders who received ASP for a period of 10 days had longer survival durations than did other responders. Remission did not continue long enough with our protocol, although a high CR rate was achieved. We conclude that the design of consolidation and maintenance therapy must be improved in order to obtain a longer duration with our protocol.
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PMID:[Treatment of adult acute lymphoblastic leukemia with Ad-VP-L regimen]. 202 Jan 19

Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance.
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PMID:Cross-resistance patterns in ACNU-resistant glioma sublines in culture. 207 67

Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.
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PMID:Treatment of adult acute lymphoblastic leukaemia. 232 50

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4-hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.
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PMID:Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia. 244 78

From 1984 to 1987, 144 previously untreated children with low (LR) or intermediate-risk (IR) acute lymphoblastic leukemia (ALL) were entered in the protocol L 841 or I 841, respectively. The patients in the LR group were randomized to receive regimen A (L 841 A) or B (L 841 B) and the patients in the IR group were randomized to receive regimen B (I 841 B) or C (I 841 C). L 841 A consisted of vincristine (VCR) + prednisone (PDN) for the remission induction phase and 18 Gy cranial irradiation combined with intrathecal methotrexate (MTX) for the central nervous system (CNS) leukemia prophylaxis. The maintenance phase consisted of MTX iv alternating 5-day course of VCR + PDN + 6-mercaptopurine (6MP) at 2 wk-interval. In L 841 B, I 841 B and I 841 C, asparaginase (ASP) was added as a third drug. Adriamycin (ADM) and high-dose MTX (100 mg/kg) were additionally employed in the intensive phase of I 841 C. Thirty-nine, 20, 25 and 49 eligible patients were entered in L 841 A, L 841 B, I 841 B and I 841 C, respectively. The event free survival rate in each regimen was 50.5% +/- 13.7% (M +/- SE), 100% +/- 6.0% (p less than 0.01), 72.7% +/- 9.8% and 40.7% +/- 13.2% (p less than 0.1) at 4 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of childhood acute lymphoblastic leukemia: randomized trials of protocols CCLSG-L 841 and I 841. (Phase III study). Children's Cancer and Leukemia Study Group]. 268 82

From May 1979 to March 1983, 76 evaluable patients with lymphoblastic lymphoma (LBL) were treated by members of the Pediatric Oncology Group (POG). Forty-six children treated by the six-drug A-COP+ regimen (Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], vincristine, prednisone, cyclophosphamide, methotrexate, and hydrocortisone) were compared in a prospective randomized trial with 30 patients receiving the modified ten-drug LSA2-L2 (cyclosphosphamide, vincristine, methotrexate, Daunomycin [daunorubicin cerubidine; Wyeth Laboratories, Philadelphia], prednisone, cytarabine, thioguanine, asparaginase, hydroxyurea, and carmustine) regimen. After adjusting for stage (I and II v III v IV), there was no statistically significant difference (P = .19) between A-COP+ and LSA2-L2 regimens on the basis of 3-year survival and disease-free survival (62% v 72% and 53% v 58%, respectively for the two treatment regimens) but the power of analysis and thus the ability to detect a clinically meaningful difference in the outcome with the two regimens was limited by the small number of patients. Neither therapy was effective for most patients with stage IV disease, with failure occurring in six of seven children receiving A-COP+ regimen and eight of 11 patients receiving LSA2-L2. Although the LSA2-L2 regimen was more toxic during the induction of remission, the toxicity during maintenance was acceptable and similar for both treatments. CNS relapse was not a significant problem whether cranial radiation with intrathecal (IT) therapy (A-COP+) or IT therapy alone (LSA2-L2) were used. Our results confirm the overall effectiveness of the LSA2-L2 regimen in children with LBLs, especially those initially free of bone marrow or CNS involvement, but were inconclusive as to the inferiority or superiority of this regimen over the A-COP+ regimen.
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PMID:Lymphoblastic lymphoma in children--a randomized trial comparing LSA2-L2 with the A-COP+ therapeutic regimen: a Pediatric Oncology Group Study. 327 50

The tremendous progress that has been made in the chemotherapy of malignant diseases since the early 1950's has enabled the cure of a significant number of cancers such as chloriocarcinoma, Burkitt's lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, the acute leukaemias, testicular carcinoma, and many childhood cancers such as rhabdomyosarcoma, Wilm's tumor, Ewing's sarcoma, ovarian cancer, and retinoblastoma. As a result, the mortality from cancers has dropped by 15% for persons under the age of 45 years and even more for those under 30 years of age. Many other metastatic cancers can now be successfully controlled with chemotherapy and, ultimately, more will be added to the growing list of curable cancers. The chemotherapeutic agents responsible for the cures of some cancers include asparaginase, actinomycin D, Adriamycin, bleomycin, cisplatin, cyclophosphamide, cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate, nitrogen mustard, prednisone, procarbazine, and vincristine. The discovery of new effective drugs such as AMSA and anthracenedione promises to improve the success rates obtained with present therapy. Chemotherapy is indicated for every patient who has metastatic cancer, since virtually every patient can receive some palliation from such therapy, while for some patients chemotherapy holds the promise of prolongation of life or even cure.
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PMID:The curability of advanced cancers with chemotherapy. 627 28


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