Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adults with previously treated acute nonlymphocytic leukemia received either 5-azacytidine or guanazole in a randomized study. Eighteen patients were treated with 5-azacytidine at a dosage of 200-250 mg/m2/day X 5 intravenously (i.v.) and six achieved a remission (five complete). The median duration of complete remission was 100 days. Among the 12 patients who received guanazole, at a dosage of 25-30 g/m2/day X 5 by continuous i.v. infusion, only one partial remission ensued. Pm 600 WBC/mm3) than nonresponders (median 1700 WBC/mm3). Both the time taken to reach the nadir white blood coung (median, 14 days) and theduration of the nadir (median, 17 days) were long after each course of 5-azacytidine, particularly for those patients who achieved a remission. Principal toxicities seen after 5-azacytidine administration were gastrointestinal tolerance, fever, and neuromuscular toxicity. Fever was the principal toxicity observed after guanazole therapy; one patient developed erythema nodosum with arthralgias and another, recurrent pulmonary infiltrates. Survival from the start of therapy was clearly longer for the patients receiving 5-azacytidine (median 140 days) because of the prolongation of survival seen in the responding patients (median 266 + days). 5-Azacytidine has significant activity as an induction agent in adults with acute nonlymphocytic leukemia, but guanazole does not appear to be of particular value for patients with this disease.
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PMID:A comparative clinical trial of 5-azacytidine and guanazole in previously treated adults with acute nonlymphocytic leukemia. 5 27

Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.
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PMID:5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. 6 73

The pyrimidine analog, 5-azacytidine (NSC 102816), was administered by continuous intravenous infusion in Ringer's lactate in increasing doses to sets of patients with metastatic cancer to establish a dose sufficient to produce mild toxicity. Twenty-one patients (23 trials) were treated with doses of 50-200 mg/sq/m/day for 5 days every 2-4 wk. Nausea and vomiting were moderate and easily preventable. Doses of 100-200 mg/sq/m for 5 days every 14 days produced granulocytopenia, usually after two courses. Less toxicity was observed when courses were given every 21-28 days. Forty-five patients with previously treated and refractory acute myeloblastic leukemia were treated. The majority received doses of 150 mg/sq m for 5 days every 2 wk. Eleven (24%) complete remissions and four partial remissions were observed. The number of courses to achieve remission averaged three and required an average of 59 days. Nine patients with blastic crisis of chronic myeloblastic leukemia and four with refractory acute lymphoblastic leukemia failed to respond. 5-Azacytidine administered by continuous infusion is well tolerated and is an active compound in acute myeloblastic leukemia.
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PMID:5-Azacytidine (NSC 102816): a new drug for the treatment of myeloblastic leukemia. 6 Jan 56

Azacitidine has been undergoing clinical trials for almost 20 years and is internationally considered to have a useful place in the treatment of acute nonlymphocytic leukemia. However, its role in the various combinations for induction, intensification, maintenance, or relapse regimens has not yet been clearly defined. This review outlines the last 10 years' clinical experience with the drug in acute nonlymphocytic leukemia, analyzes what critical information has yet to be obtained, and suggests what phase III trials may still be feasible to gather that information.
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PMID:Azacitidine: 10 years later. 244 May 70

Several new cytostatic drugs have entered clinical Phase I-II studies for treatment of leukemia: most promising are pyrimidine analogues such as 5-Azacytosine arabinoside, 5-Aza-2-deoxycytidine, 5-Azacytidine, cyclocytidine, and 2'-2'-difluorodeoxycytidine. They act on different biochemical levels towards DNA-synthesis. Fludarabine is a purin analogue and seems very active in treating CLL. Tiazofurin is an antimetabolite counter-acting nicotinic acid with most promising activity in CML blast crisis. Other substances include deoxycoformycin, an adenosine analogue for treatment of T-cell neoplasias, 1, 25-dihydroxy vitamin D 3 as differentiation inducer, and homoharringtonine, an alkylating agent widely used for treating de novo AML in China. New anthracyclines are THP-adriamycin, fluoroadriamycin, and 4-demethoxydaunorubicin. Amsacrine (mAMSA) finally, is a synthetic aminoacridine with DNA-intercalating properties. The intact acridine ring appears essential for antitumor activity. The plasma clearance of both total amsacrine and unchanged parent species is biphasic. There is a considerable influence of hepatic and renal impairment on plasma clearance. Clinical toxicities include marked myelosuppression, gastrointestinal symptomes, phlebitis, mucocutaneous lesions, occasionally alopecia and neurotoxities. It is a very active drug, particularly in treating AML. Studies using mAMSA alone or in combination revealed comparable results to the anthracyclines. The E.O.R.T.C. Leukemia Cooperative Group has used successfully mAMSA in several trials: relapsed and refractory AML, intensive maintenance treatment during first remission in AML, and, still on-going, during intensive consolidation randomized against BMT in AML-patients under the age of 45 years, and randomized against standard consolidation between the age of 45 and 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New drugs in the treatment of acute and chronic leukaemia: current role of mAMSA. 269 2

11 patients (aged 23--75 years) with refractory acute leukemia were treated at the Maine Medical Center with 5-Azacytidine, 150 mg/m2/day, by continuous infusion for 5 days every 2 weeks. Prior therapy included anthracycline/cytosine arabinoside protocols. Of the 8 patients with refractory de novo acute myelogenous leukemia, 6 achieved remission at an overall response rate of 75% (3 complete remission and 3 partial remission). An average of 1.67 courses was necessary to achieve a response. Remissions were not seen in blastic chronic myelogenous leukemia nor in acute leukemia secondary to cytotoxic drugs. Toxicity included myelosuppression, moderate nausea and vomiting, abnormal liver function tests, and neuromuscular symptoms. 5-Azacytidine by continuous infusion has significant activity in refractory acute myelogenous leukemia and should be considered for inclusion in primary remission induction therapy.
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PMID:5-azacytidine in refractory acute leukemia. 617 65

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with an invariably fatal outcome. Other than bone marrow transplantation, no treatment has been able to alter the natural history of MDS. As a result, there has been an interest in identifying new and more effective chemotherapeutic agents. Many of the drugs that have been evaluated in an attempt to increase remissions and prolong survival were selected because of their activity in acute myeloid leukemia. Thus cytarabine has been the most widely studied drug. Although numerous studies suggested activity for low-dose cytarabine (LoDAC), a careful analysis of the data identified a complete remission (CR) rate of less than 20%, without meaningful clinical benefit. The issue of LoDAC was finally put to rest by a randomized trial in which survival was no better than with supportive care. 5-Azacytidine induces cellular differentiation by hypomethylation of DNA. Phase II trials noted CRs in fewer than 10% of patients, with response rates under 30%, although additional patients appeared to experience hematologic and clinical benefit. A randomized trial of 5-azacytidine versus supportive care failed to demonstrate a survival benefit. One of the most promising new agents is the topoisomerase inhibitor topotecan, which achieves CRs in more than 30% of patients. Combinations of this drug with other active agents are in development. Obviously, new treatment strategies are needed to improve the outcome of MDS patients. Combination approaches incorporating new, active agents should have sound scientific rationale, targeting biological differences among the various MDS subtypes.
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PMID:Standard and low-dose chemotherapy for the treatment of myelodysplastic syndromes. 973 95

5-Azacytidine was first synthesized almost 40 years ago. It was demonstrated to have a wide range of anti-metabolic activities when tested against cultured cancer cells and to be an effective chemotherapeutic agent for acute myelogenous leukemia. However, because of 5-azacytidine's general toxicity, other nucleoside analogs were favored as therapeutics. The finding that 5-azacytidine was incorporated into DNA and that, when present in DNA, it inhibited DNA methylation, led to widespread use of 5-azacytidine and 5-aza-2'-deoxycytidine (Decitabine) to demonstrate the correlation between loss of methylation in specific gene regions and activation of the associated genes. There is now a revived interest in the use of Decitabine as a therapeutic agent for cancers in which epigenetic silencing of critical regulatory genes has occurred. Here, the current status of our understanding of the mechanism(s) by which 5-azacytosine residues in DNA inhibit DNA methylation is reviewed with an emphasis on the interactions of these residues with bacterial and mammalian DNA (cytosine-C5) methyltransferases. The implications of these mechanistic studies for development of less toxic inhibitors of DNA methylation are discussed.
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PMID:5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. 1215 9

Azacitidine, a pyrimidine analogue, is an antineoplastic agent that acts mainly by causing hypomethylation of cytosine residues in newly replicated DNA and has shown efficacy in the treatment of myelodysplatic syndromes (MDS). In a randomised controlled trial in patients with MDS (n=191), subcutaneous azacitidine 75-100 mg/m2/day in 7-day cycles every 28 days with continuing supportive care produced a significantly higher response rate (including reductions in rate of transformation to acute myeloid leukaemia and transfusion requirements) than that seen with supportive care alone (60% vs 5%; p<0.001). Patients (n=49) who were switched from supportive care to azacitidine after 4 months also showed a 47% response rate. The clinical response in patients receiving azacitidine was associated with significant (p<or=0.015) improvements in several measures of health-related quality of life, including those assessing fatigue and physical functioning, compared with those in supportive care recipients. Given the grim prognosis of MDS patients, azacitidine was generally well tolerated, with common, but transient, myelotoxicity. Adverse events did not increase in severity or frequency during the course of the treatment.
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PMID:Azacitidine: in myelodysplastic syndromes. 1611 77

For patients with acute myeloid leukemia refractory to intensive chemotherapy prognosis is very poor and treatment options are limited. 5-Azacytidine, a demethylating drug, is effective in the treatment of myelodysplastic syndromes when administered at a low-dose, subcutaneously. We report a case of a patient with AML refractory to induction chemotherapy as well as to two high-dose salvage regimens. The patient achieved CR through monotherapy with low-dose azacytidine.
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PMID:Induction of complete remission in a patient with acute myeloid leukemia refractory to high-dose chemotherapy through treatment with 5-azacytidine. 1689 Feb 86


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