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

Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic. It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells. The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule. Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin. Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours. Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML. Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine. In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced. Anorexia, mild nausea and infrequent vomiting were observed. Myelosuppression was common but dose reduction was not necessary. There was no alopecia and no congestive heart failure.
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PMID:Aclarubicin: experimental and clinical experience. 391 80

A Phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was conducted in 162 patients with various hematological malignancies in a multi-institutional cooperative study. THP was given intravenously at a dose of either 10-30 mg/body for 3-5 consecutive days or 40-60 mg/body at 3-week intervals. Of 22 patients with AML, complete remission (CR) was observed in 2 patients and partial remission (PR) in 2. Of 18 patients with ALL, CR was observed in 5 and PR in 3. Of 68 patients with NHL, CR was observed in 11 and PR in 22. Of 8 patients with HD, CR was observed in 4 and PR in 2. One CML case showed CR and one ATL case showed PR. PR was noted in one of 2 patients with mycosis fungoides. Overall remission rate was 43.1% (CR 23 cases and PR 33 cases). The predominant toxicity was myelosuppression. Leukopenia (less than 4,000/mm3) was noted in 67 (77.6%) and thrombocytopenia (less than 10 X 10(4)/mm3) in 24 (27.0%). Nausea/vomiting and anorexia were common, and were observed in 61 (43.3%) and 65 (46.1%) cases, respectively. Hair loss and cardiotoxicity were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for various hematological malignancies including acute leukemia and malignant lymphoma.
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PMID:[A phase II study of (2''R)-4'-0-tetrahydropyranyladriamycin (THP) in patients with hematological malignancies. THP Study Group]. 394 12

This study tested the efficacy of rubidazone in the treatment of recurrent acute leukemia in children. In the first phase of this study, rubidazone was administered in a dose of 450 mg/m2 to 26 children with acute lymphocyte leukemia (ALL) and to 8 children with acute nonlymphocytic leukemia (ANLL) in relapse. In children with ALL, 6 patients (23%) achieved a complete remission (CR) and an additional 4 patients (15%) achieved a partial remission (PR). Of 8 children with ANLL, 2, (25%) achieved a CR, and an additional patient achieved a PR. Because of the moderate to severe toxicity of rubidazone, the next phase of the study consisted of randomizing patients between a dose of 450mg/m2 and 300 mg/m2 of rubidazone. In children with ALL in their first relapse who were not resistant to Adriamycin (doxorubicin), 7 of 10 patients (70%) achieved a CR with 450 mg/m2 of rubidazone, whereas 2 of 12 patients (17%), achieved a CR with 300 mg/m2 (P less than 0.04). In children with ALL in their first relapse but resistant to Adriamycin, 3 of 17 patients (18%) achieved a CR with 450 mg/m2, and 2 of 17 patients (12%), acheived a CR with 300 mg/m2. This study suggests that rubidazone is capable of inducing remission in children with ALL in relapse. The main toxicity of rubidazone consisted of severe and prolonged myelosuppression resulting in fever and infection. This toxicity was not significantly decreased by reducing the dose of rubidazone from 450 mg/m2 to 300 mg/m2. Fatal cardiac toxicity was observed in 3 children.
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PMID:Rubidazone in the treatment of recurrent acute leukemia in children. A Pediatric Oncology Group Study. 394 26

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.
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PMID:Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients. 397 58

Reinduction therapy consisting of cyclophosphamide (250 mg/m2 orally daily for 4 days) followed by etoposide (250 mg/m2 iv daily for 3 days) was administered to 14 children with refractory or recurrent acute nonlymphocytic leukemia. Five complete remissions were achieved in eight patients who had relapsed in the bone marrow 1-27 months after cessation of initial therapy, which included anthracyclines, cytarabine, etoposide, and 5-azacitidine. Reinduction attempts were unsuccessful in patients who had failed to achieve an initial remission and in those whose relapses occurred while receiving therapy. Toxicity, including myelosuppression and mucositis, was within acceptable limits. This drug combination deserves further assessment in therapeutic protocols for patients with acute nonlymphocytic leukemia.
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PMID:Cyclophosphamide/etoposide: effective reinduction therapy for children with acute nonlymphocytic leukemia in relapse. 401 96

A combination therapy with 5 aza-cytidine (5 AZA-C), vincristine (VCR), and prednisone (PRED) was given to 53 children with acute nonlymphocytic leukemia resistant to conventional therapy. Of these, eight children obtained a complete remission and seven a partial remission. Maintenance therapy was initiated in 12 children. The remission duration varied between 19 and 176 days (median 69 days). The main toxicity was vomiting and myelosuppression manifested as severe neutropenia and thrombocytopenia. It is concluded that VCR and PRED do not increase the response rate to that of 5 AZA-C as a single agent.
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PMID:Low response rate to 5 aza-cytidine, vincristine, and prednisone therapy in previously treated childhood acute nonlymphocytic leukemia: a Southwest Oncology Group Study. 616 89

Twenty-nine adults with advanced acute nonlymphocytic leukemia were treated with an intensive chemotherapy program consisting of 5-azacitidine and zorubicin. Overall, eight patients (28%) achieved a complete remission. Although only one of 19 patients with refractory leukemia responded, seven of ten patients who were treated immediately following relapse from a prior remission achieved another complete remission. The duration of remission ranged from 5 to 33 weeks (median, 14). Treatment resulted in severe toxic reactions including myelosuppression, renal tubular dysfunction, and elevations in liver enzymes. In addition, each of the 15 patients who died of treatment-associated complications had a severe infection. This combination of 5-azacitidine and zorubicin is relatively ineffective for truly refractory leukemia, but it may be a useful alternative following relapse.
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PMID:5-azactidine and zorubicin for patients with previously treated acute nonlymphocytic leukemia: a Cancer and Leukemia Group B pilot study. 617 30

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

5 children with acute nonlymphocytic leukemia in relapse who had received 5-azacytidine as a part of previous multiagent chemotherapy received continuous infusion of 5-azacytidine, 150-200 mg/m2/day, for 5-7 days every 2 weeks. 2 achieved remission marrows with good peripheral counts (duration 1 and 3 months). 1 achieved a transient remission marrow but remained pancytopenic and 1 achieved reduction from 91% blasts to 18% blasts in the marrow. Principal toxicities were severe myelosuppression, diarrhea, and phlebitis.
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PMID:Continuous infusion of 5-azacytidine as induction for acute nonlymphocytic leukemia in patients with previous exposure to 5-azacytidine. 618 42

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63


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