Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antitumor drugs, like any other therapeutic agent, have the ability to incite hypersensitivity reactions. Certain of such drugs (e.g., L-asparaginase and taxol) cause reactions with great enough frequency to be a major impediment to repetitive use of the drug. Very few antitumor drugs have not had at least one reported instance of causing a hypersensitivity reaction. Most reactions are of the type I category in the Gell and Coombs classification, but there also are instances of types II, III, and IV reactions caused by many of the antineoplastic agents. The mechanisms of such reactions have been poorly evaluated in many reports. In analyzing a hypersensitivity reaction in a patient being treated for cancer, one should document that the antitumor drug is indeed the offender, and not an ancillary drug or a formulation product that is being used. There are many tests that evaluate the source and mechanism of hypersensitivity reactions. This article reviews the current information on hypersensitivity reactions to antineoplastic drugs and provides a logical approach for their assessment.
Cancer Metastasis Rev 1987
PMID:Hypersensitivity reactions from antineoplastic agents. 331 75

Fifty-eight dogs with lymphoma were treated with combination chemotherapy (vincristine, cyclophosphamide, L-asparaginase, and doxorubicin HCl [VCAA]) followed by intralymphatic autochthonous tumor cell vaccine (CI). Thirty dogs received chemotherapy alone (VCAA). There was no overall significant difference in survival times between the two groups, although there was a trend toward prolonged survival in the CI group. Asymptomatic dogs (Stage A) and dogs less than 7 years of age with Stage A disease treated with CI had significantly longer survival. Dogs treated with CI had a significantly longer first remission. Regardless of treatment group, male dogs had significantly longer remission times compared with female dogs.
Cancer 1988 May 15
PMID:Chemotherapy versus chemotherapy with intralymphatic tumor cell vaccine in canine lymphoma. 335 2

The effects of vincristine (VCR) in combination with methotrexate (MTX) and other antitumor agents were evaluated by cell growth inhibition assay using a human acute lymphoblastic leukemia cell line (MOLT-3). The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity (G. G. Steel and M. J. Peckman, Int. J. Radiat. Oncol., 5:85-91, 1979). Simultaneous exposure of VCR and MTX produced subadditive or mutually protective interactions. Sequential exposure to VCR first followed immediately by MTX produced similar interactions. When the interval of VCR exposure first and then MTX was increased from 0 to 3, 8, and 24 h, the inhibition of cell growth moved from protection and subadditivity to additivity only. The reversed order of exposure to the 2 drugs produced an entirely different picture. Thus, when the interval of MTX exposure first followed by VCR increased from 0 to 3, 8, and 24 h, the inhibitory effects of the combination changed progressively from the area of subadditivity to the area of supraadditivity. When these data were evaluated using median effect plot analyses (T-C. Chou and P. Talalay. In: New Avenues in Developmental Cancer Chemotherapy, pp. 36-64. Orlando, FL: Academic Press, 1987), strongly synergistic interaction of this sequence at space intervals was confirmed. These data show that the synergistic effects were produced only when MTX was followed 8 or 24 h later by VCR. Other schedules were only additive or even antagonistic. Simultaneous exposure of VCR with daunorubicin, 1-beta-D-arabinofuranosylcytosine, or bleomycin also had subadditive and protective effects. VCR, followed by daunorubicin with the interval of 24 h and vice versa, was again subadditive and protective. VCR, followed by 1-beta-D-arabinofuranosylcytosine with the interval of 24 h and vice versa, was again subadditive or additive only. Simultaneous and continuous exposures of VCR with vinblastine or L-asparaginase were only marginally supraadditive.
Cancer Res 1988 Jan 15
PMID:Effects of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture. 342 52

Methotrexate (MTX) and L-asparaginase (ASP) are effective agents in the treatment of acute lymphoblastic leukemia (ALL). The effects of combining MTX and ASP are schedule dependent. To investigate this schedule dependency, the Cancer and Leukemia Group B (CALGB) employed vincristine and prednisone with progressive dose escalation of moderate-dose MTX (125 mg/m2) followed 24 h later with ASP (6,000 U/m2) in refractory adult ALL. We treated 38 patients with refractory or first relapse adult ALL. Most patients had received prior ASP (92%) and MTX (72%). A complete remission was achieved in 25% with a median duration of remission of 21 weeks. The median survival for the entire group was 7.4 months. Therapy was well tolerated and toxicity was acceptable. Our response rate was lower than other tandem MTX and ASP adult ALL trials. Therapy was similar with other series, with the exception of the dose of ASP employed. We conclude that tandem MTX and ASP, in the doses and schedule used here, has only modest activity in previously treated adult ALL. This regimen offers little advantage to other salvage regimens.
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PMID:Therapy of refractory adult acute lymphoblastic leukemia with vincristine and prednisone plus tandem methotrexate and L-asparaginase. Results of a Cancer and Leukemia Group B Study. 346 28

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.
Eur J Cancer Clin Oncol 1987 May
PMID:Treatment of the lymphoid blast crisis of chronic myeloid leukemia. 347 57

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.
Cancer 1987 Nov 15
PMID:Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia. 349 11

Protein C is, after activation by thrombin, a potent inhibitor of blood coagulation. An isolated deficiency of protein C increases the risk of thrombosis. The two forms of protein C deficiency, the heterozygous and the homozygous deficiency state, have different clinical features. Patients with heterozygous protein C deficiency are at a high risk to develop venous thrombosis and pulmonary embolism. In newborns with homozygous protein C deficiency with very low protein C levels (1%) a purpura fulminans like syndrome was observed. Heparin and coumarin derivatives are effective drugs in heterozygous protein C deficiency, homozygous patients may be treated either by replacement of protein C or coumarin derivatives. Decreased protein C levels were observed in various other diseases: Chronic and acute liver disease, disseminated intravascular coagulation, malignancy, postoperatively and during treatment with asparaginase. The role of protein C in these diseases to trigger thrombosis is not yet established.
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PMID:Clinical relevance of protein C. 352 11

Luminol-dependent chemiluminescence of whole blood (whole blood CL) was developed to estimate the phagocytic function of granulocytes and the serum opsonin activity simultaneously. Whole blood (0.1 ml) was examined directly and results were obtained within 20 minutes. Phagocytic function of granulocytes can be estimated from the peak CL of whole blood and the number of granulocytes in a specimen, and the opsonin activity from the amount of time the peak CL is shown after the addition of nonopsonized CL inducer (nonopsonized zymosan). Subsequently, whole blood CL was measured to evaluate phagocytic functions in children with disease. Patients with chronic granulomatous disease showed no CL, and one of their mothers (1/3) showed low CL, suggesting she is a carrier. Two patients with hypocomplementemia (SLE and chronic nephritis) showed low serum opsonin activity, and phagocytic function of their granulocytes was enhanced. In cord blood and newborn infants serum opsonin activity was low, and phagocytic function of granulocytes was slightly decreased in cord blood but not in newborn infants. Patients with systemic bacterial infections showed an increased phagocytic function of granulocytes. Anti-cancer drugs decreased serum opsonin activity in children with leukemia or lymphoma. The children treated with L-asparaginase had very low opsonin activity, suggesting the drug inhibits complement synthesis. The measurement of whole blood CL was useful for monitering the phagocytic functions of blood after granulocyte transfusion.
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PMID:[Chemiluminescence of whole blood--analysis of the kinetics and application of clinical examination of phagocytic functions of whole blood from various type of diseases]. 355 74

Thirty-seven dogs with malignant lymphoma were treated with either polyethylene glycol conjugated (PEG) asparaginase alone (10-30 IU/kg intraperitoneally [IP] weekly--20 dogs) or PEG-asparaginase combined with one cycle of chemotherapy (vincristine, cyclophosphamide, methotrexate, and prednisone), followed by maintenance PEG-asparaginase (30 IU/kg, IP weekly--17 dogs). In the 20 dogs (eight were chemotherapy resistant) treated with PEG-asparaginase alone, seven had a complete response (CR), seven had a partial response (PR), five had no response (NR), and one was not evaluable (NE). The duration of response (CR + PR) ranged from 14 to 102 days (median, 48 days). In the eight chemotherapy-resistant dogs (seven were previously resistant to L-asparaginase) four had responses (one CR and three PR). In the 17 dogs treated with combined PEG-asparaginase and chemotherapy, 13 had a CR, two had a PR, and two had NR. None of the dogs had had prior chemotherapy, and the duration of response (CR + PR) ranged from 7 to 840+ days, with a median of 126+ days. Four dogs are still on maintenance PEG-asparaginase at 16+, 21+, 26+, and 28+ months. Toxicity consisted of death due to massive tumor breakdown (two dogs), disseminated intravascular coagulation (DIC--one dog), hypersensitivity reaction (one dog), vomiting (three dogs) and soft stools (three dogs). Four normal dogs were given very high doses of PEG-asparaginase (200 IU/kg and 1200 IU/kg) once weekly for two treatments without any significant toxicity. These results indicate that PEG-asparaginase has antitumor activity in dog with spontaneously occurring malignant lymphoma.
Cancer 1987 Jun 15
PMID:A preliminary study on the evaluation of asparaginase. Polyethylene glycol conjugate against canine malignant lymphoma. 356 63

A case of an 18-year-old woman with acute lymphoblastic leukemia who developed L-asparaginase-associated stroke and subclavian vein thrombosis is presented. The latter was also associated with a Hickman central venous catheter. Thrombotic complications occurred when plasma levels of plasminogen and antithrombin III were still markedly reduced as a result of L-asparaginase therapy, although the fibrinogen had recovered from its lower levels. The stroke was treated with fresh frozen plasma and the subclavian vein thrombosis was treated with streptokinase and fresh frozen plasma. L-asparaginase and Hickman-associated coagulopathy is reviewed and the treatment is discussed.
Cancer 1985 Feb 15
PMID:Thromboembolic complications associated with L-asparaginase therapy. Etiologic role of low antithrombin III and plasminogen levels and therapeutic correction by fresh frozen plasma. 385 65


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