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)

Of the many high-dose Ara-C regimens that have been proposed, the one published by Herzig [24] has been applied most widely. Every 12 h patients receive 3 g/m2 Ara-C for 75-90 minutes for a total of 12 doses. Using that regimen, 25% of patients with refractory acute myelogenous leukemia (AML) and 60% of patients in untreated relapse achieve a complete remission (CR). With few exceptions, complete remissions are obtained after one cycle, median remission duration is between 4 and 6 months. Consolidation or maintenance therapy was not usually given. Currently, numerous modifications of that regimen are under investigation: combinations with other cytostatic agents like anthracyclins, m-AMSA, vincristine; the Capizzi-regimen and intermediate dose Ara-C. Preliminary results of those trials are promising but need to be confirmed by other groups. This survey does not comment on Ara-C toxicity and on Ara-C treatment of CNS leukemia, which are both reviewed in two further articles of this issue.
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PMID:[Results of high-dose cytarabine therapy. A review]. 388 25

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.
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PMID:High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia. 623 99

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.
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PMID:[Phase II study of AMSA in adults with acute therapy-refractory leukemias]. 635 48

Amsacrine (AMSA) has been shown to be an effective therapeutic agent in the treatment of adult acute nonlymphocytic leukemia (ANLL). The Eastern Cooperative Oncology Group studied the efficacy and toxicity of high-dose amsacrine (200 mg/m2/day for 5 days) in 38 adult patients with refractory and relapsed ANLL. The complete remission rate was low (8%). This dose level of amsacrine caused severe mucositis in 24% of patients and marked liver function abnormalities in 11%. Seizures did not occur, and two reversible cardiac events were not clearly attributable to amsacrine administration. Escalation of amsacrine beyond currently recommended total doses of 600-750 mg/m2 is unlikely to be of benefit.
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PMID:High-dose amsacrine (AMSA) therapy of relapsed and refractory adult acute nonlymphocytic leukemia. A phase II study. 654 66

A phase II pilot study of amsacrine in refractory adult acute leukemia was conducted by the Southeastern Cancer Study Group from May 1979 to August 1980. Amsacrine, 90 mg/m2, was given daily for 5-8 days to 45 patients with acute myeloblastic leukemia, 15 patients with acute lymphoblastic leukemia, and six patients with blastic transformation of chronic granulocytic leukemia. Of the 66 patients entered in the study, 59 (89%) were evaluable for response. Complete remissions were observed in eight of 41 evaluable patients with acute myeloblastic leukemia (20%) and in three of 12 with acute lymphoblastic leukemia (25%). Remissions were short-lived (median, 7.9 weeks; range, 2-27). Toxic effects included the expected myelosuppression (100%), as well as moderate to severe stomatitis (46%), hyperbilirubinemia (30%), and supraventricular tachycardia (1.5%). This cooperative group pilot study confirms previous reports from single institutions that amsacrine is a useful drug in the treatment of refractory adult acute leukemia and is worthy of further study.
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PMID:Amsacrine in refractory adult acute leukemia: a pilot study of the Southeastern Cancer Study Group. 658 70

The relationship between cell growth inhibitory effects and terminal differentiation-inducing effects of nine clinically active chemotherapeutic agents was evaluated using HL-60, a human acute myelogenous leukemia cell line. Continuous exposure to HL-60 cells of adriamycin, daunorubicin, mitoxantrone, m-AMSA, cytosine arabinoside, 6-thioguanine (6-TG), actinomycin-D (Act-D) and vincristine resulted in percentage increase of morphologically differentiated cells and phagocytic cells. Hydrocortisone at a concentration of up to 10(-4) M failed to produce this effect. Examination of actual numbers per flask of morphologically differentiated cells and phagocytic cells revealed, however, that all these agents except Act-D and 6-TG failed to produce a numerical increase in differentiated cells in comparison with those of control groups at day 6. Only Act-D and 6-TG were able to produce increases in the percentage, as well as actual number, of differentiated cells. These data indicate that the percentage increase in terminal differentiation-induced cells by certain chemotherapeutic agents is due not to their ability to increase differentiated cells but to their ability to inhibit the growth of primitive cells preferentially.
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PMID:[Differential cell growth inhibition and terminal differentiation induction by chemotherapeutic agents of a human acute myelogenous leukemia cell line (HL-60) in vitro]. 659 56

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
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PMID:Phase I study of m-AMSA in patients with solid tumors and leukemias. 689 83

The current status of three drugs of clinical interest to the National Cancer Institute is reviewed. m-AMSA, a drug with a wide spectrum of activity in murine tumors, is now in phase II trial and has shown itself to have a high order of activity in acute nonlymphocytic leukemia. Dihydroxyanthracenedione, a compound with some of the characteristics of anthracyclines but with no cardiac toxicity in animal toxicology studies, is in phase I evaluation. Deoxycoformycin, an adenosine analog which is a potent inhibitor of adenosine deaminase, has shown moderate activity in acute leukemia patients in phase I trials, and has the potential to produce synergistic antitumor toxicity when used with arabinofuranosyladenine.
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PMID:Current status of clinical trials of m-AMSA, dihydroxyanthracenedione, and deoxycoformycin. 697 70

Acute myeloid leukemia (AML) is frequently encountered in elderly patients (> 65) whereas most myelosuppressive chemotherapy protocols are restricted to younger patients. We retrospectively reviewed the 21 patients older than 65 (median age: 70, range: 66-86) hospitalized in our leukemia unit for recently diagnosed AML between 1. 1. 1988 and 31. 3. 1993. 16 had de novo AML (n-AML) and 5 had AML secondary to myelodysplastic syndromes (s-AML). Induction therapy consisted of cytarabine and either daunorubicine or mitoxantrone at conventional dosage in 18/21 patients. Early consolidation therapy was given to 14/21 patients and consisted of m-AMSA and VP-16 in 11 of them. The response to, and toxicity from, myelosuppressive chemotherapy was different according to the type of AML. In patients with n-AML a complete remission (CR) was obtained in 63% (10/16) and only 19% (3/16) died of MCT-related toxicity. In contrast, only 1/5 patients with s-AML achieved CR while 4/5 died of toxicity. The median duration of CR was 40 weeks (range: 5-147+) and median overall survival 23 weeks (range: 1-211+), with an estimated 3-year overall survival rate of 9.5% (2/21). Overall survival of patients with n-AML was significantly longer than that of patients with s-AML (p < 0.05). Hospital stay in relation to survival time was 100% for patients with s-AML, 49% for patients with n-AML not achieving CR and 25% for patients with n-AML with CR. In conclusion, elderly patients with AML can benefit from myelosuppressive chemotherapy providing they present with de novo AML.
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PMID:[Should patients over 65 years old with acute myeloid leukemia be treated with myelosuppressive chemotherapy?]. 789 71


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