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)

Mitoxantrone in combination with VP-16 proved to be effective in refractory and relapsed acute myeloid leukemia (AML), with 42% of patients achieving complete remission (CR). The aim of this study was to assess whether the addition of cytosine arabinoside increased the response rate at a tolerable toxicity. The regimen consisted of mitoxantrone (M) 10 mg/m2 i.v. days 4-8, cytosine arabinoside (A) 100 mg/m2 continuous infusion days 1-8, and etoposide (VP-16) (V) 100-120 mg/m2 i.v. days 4-8 (MAV protocol) for relapsed and refractory AML. Thirty-six patients were treated, with a median age of 51 (20-73) years. For induction therapy one to two MAV cycles and for consolidation therapy two courses were scheduled. Twenty-one (58.3%) patients attained a complete remission (CR), with a median duration of 4.5 (1-12+) months. The median survival of all patients was 5.5 (0.5-15.5+) months. Four patients died in CR from chronic infections or after consolidation therapy with MAV. In evaluable patients, times to greater than 500 granulocytes/microliters and greater than 25,000 platelets/microliters were 23 (7-46) and 23 (6-44) days, respectively. In 54 evaluable MAV courses the following toxicity was observed (WHO grades 3/4): 26%, nausea and vomiting: 9%, hemorrhage; 6%, bilirubinemia; 11%, diarrhea; 22%, mucositis; 6%, local infection; 20%, septicemia; 13%, fever of unknown origin; 2%, cardiac arrhythmia; 7%, congestive heart failure. We conclude that MAV therapy is a highly active antileukemic combination with acceptable toxicity, which is recommended for further clinical trials in untreated AML.
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PMID:Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia. 218 26

Idarubicin is a new derivative of Daunorubicin which was found to be more potent and more active than Daunorubicin and Doxorubicin in several experimental leukemias. Its antileukemic activity in preclinical models prompted the introduction of Idarubicin into clinical studies. As a single agent, Idarubicin produced complete remission in 20% and 30% of patients with heavily pretreated pediatric and adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. Idarubicin combined with Cytarabine and/or other antileukemic agents produced complete remissions in 46% of patients with refractory or relapsed AML and in 58% of patients with refractory or relapsed ALL (adult and pediatric). Subsequently, Idarubicin has been employed in untreated AML patients in combination with Cytarabine and/or Etoposide, producing complete remissions in more than 80% of patients. In ALL patients the drug has been used in combination with Vincristine, Cytarabine and Prednisone, producing complete remissions in 82% of patients. Recently, Idarubicin has been utilized in combination with intermediate doses of Cytarabine in refractory or relapsed ALL and AML, and 70% of patients achieved complete remission. Preliminary results of ongoing prospective randomized studies in untreated adult AML seem indicate that Idarubicin is at least equivalent, if not superior to Daunorubicin. The antileukemic activity of Idarubicin given orally as single agent, or in combination with other drugs, has been shown in AML and myelodysplastic syndromes. The toxicity of Idarubicin includes mild nausea and vomiting, alopecia and liver dysfunction. Ongoing randomized trials comparing Idarubicin to Daunorubicin should provide more information about the potential cardiotoxicity of this drug.
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PMID:Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies. 219 43

The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis.
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PMID:Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group. 223 3

Eighty-seven consecutive children and young adults with acute nonlymphocytic leukemia (ANLL) were treated uniformly with induction chemotherapy based on daunorubicin and cytarabine (ara-C), with the addition of etoposide (VP-16) and azacytidine (5-Az) for refractory patients. Of the 65 patients who entered complete remission, 42 were eligible for assessment of response to intensive chemotherapy consisting of four pairs of drugs administered in sequential fashion. Nineteen others with available histocompatibility locus antigen (HLA)-compatible donors were assigned to receive allogeneic bone marrow transplants within 16 weeks from their dates of complete remission. Durations of continuous complete remission (CCR) in the two groups were not significantly different at a median follow-up time of 6 years (P = .30 by log-rank analysis). Kaplan-Meier estimates of CCR probabilities (+/- SE) at 6 years were 43% +/- 13% (transplantation) and 31% +/- 7% (sequential chemotherapy). Postremission failures in the sequential chemotherapy group resulted from bone marrow relapse in 23 of 29 patients (79%), whereas in the transplantation group, failures were equally divided between marrow relapse and transplantation-related complications of graft-versus-host disease (GVHD) or infection due to the immunosuppressive effects of ablative chemotherapy. Comparison of hematologic remission curves indicated a significant advantage for marrow transplantation in terms of systemic leukemia control (P = .06). Thus, in programs of intensive chemotherapy of the type described here, allogeneic marrow transplantation should be seriously considered as alternative therapy for patients in first remission who have an HLA-matched sibling donor, provided that effective methods for control of transplant-related complications are available.
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PMID:Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission. 229 72

We report our experience from a clinical trial of autologous bone marrow transplantation (ABMT) in the treatment of 30 patients with acute myeloid leukemia (AML) using monoclonal antibody (MoAb) and complement-treated bone marrow. All patients were in complete remission (CR) at the time of transplant: 6 patients were in first CR, 18 in second CR, and 6 in third CR. The median age of all patients was 42 years (range 11 to 57 years). For marrow ablation, 28 patients were treated with cyclophosphamide and total body irradiation. One patient was treated with busulfan and cyclophosphamide and one was treated with busulfan and VP-16. Each patient was then transfused with autologous bone marrow that had been harvested previously and treated with two MoAbs, PM-81 and AML-2-23, and rabbit complement. Median time to recovery of neutrophils (500/microL) was 30 days, and platelets (20,000/microL) was 45 days. Median time for initial erythrocyte engraftment, assessed by a flow cytometric reticulocyte assay, was 13 days. Median overall and relapse-free survival of first CR patients was at least 17.4 months post-ABMT and the 2- and 3-year actuarial overall and relapse-free survival was 67% (+/- 19%). Median survival for the 24 patients in second or third CR was 6.8 months post-ABMT and 9.3 months since CR; however, six patients survived disease-free from 16 to 61 months post-ABMT. For the second and third CR group it was observed that six patients (5 of the 6 survivors) showed "inversions," when their post-ABMT remission lasted longer than any previous one. Actuarial 2- and 3-year disease-free and overall survival of patients in second and third CR was 25% (+/- 9%) and 18% (+/- 9%), and 29% (+/- 9%) and 23% (+/- 9%), respectively. ABMT avoids the problems of graft-versus-host disease and of finding suitable donors for allogeneic marrow transplantation.
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PMID:Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. 230 22

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
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PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.
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PMID:High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy. 237 80

Thirty-nine patients with acute myeloblastic leukemia (AML) in first complete remission (CR) were treated by autologous bone marrow transplantation. All patients received the same induction and consolidation chemotherapy consisting of a combination of daunorubicin (DNR) and cytarabine (Ara-C) followed by four courses of DNR, Ara-C and 6-thioguanine (6-TG). Two different conditioning regimens were used; 25 patients were submitted to the BAVC regimen (BCNU, amsacrine, VP-16 (etoposide) and Ara-C) and 14 to a cyclophosphamide/total body irradiation (CY + TBI) regimen. Six patients (one treated with BAVC and five treated with CY + TBI) died in aplasia. Twelve of the 25 BAVC treated patients and one of the nine CY + TBI treated patients relapsed; 12 (48%) of the BAVC treated patients are in CR with a median follow-up of 45 months and eight (57%) of the CY + TBI treated patients are in CR with a median follow-up of 50 months. All patients in CR have survived for more than 2 years since transplant.
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PMID:Autologous bone marrow transplantation in patients with AML in first complete remission. Results of two different conditioning regimens after the same induction and consolidation therapy. 240 28

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.
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PMID:Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study. 243 59

We optimized the modulation of drug resistance by the irreversible augmentation of cytotoxicity of coincubating vinblastine (VNB) with VP-16 and the reversible increase in cytotoxicity of coincubation of verapamil (VPL) with VNB and VP-16. VPL was administered as a loading dose (i.v.) (0.15 mg/kg) and then administered as a constant infusion (0.005 mg/kg) over 6 days. 24 h after verapamil, VNB 2 mg/m2 IVP was administered and followed 1 h later by a 5-day simultaneous continuous infusion of VP-16 (200 mg/m2/day) to seven pediatric patients (11 courses) with refractory malignancies. The mean age at treatment was 7.5 +/- 5.3 years, mean prior anthracycline dose (303 +/- 210 mg/m2) with a range of 0-606 mg/m2. Toxicity was limited to cardiac and hematological. The median nadir of the WBC was 900 at 14.5 +/- 0.5 days and platelet count 32,000 at 15.5 +/- 0.8 days. There were two episodes of bacterial sepsis both of which responded to i.v. antibiotics. Five of 11 courses resulted in first-degree block and one course in second-degree block. At Hour 120 of the VPL infusion the PR interval was 0.18 +/- 0.01 versus 0.13 +/- 0.01 at Hour 0 (P less than 0.0004). The ejection fraction by two-dimensional echocardiogram was not significantly different at Hour 0, 24, or 120 of the infusion (60.6 +/- 2.7 versus 52.7 +/- 5.1 versus 51.8 +/- 5.0%). The cardiac index was also not significantly different at Hour 0, 24, or 120 (4.39 +/- 0.2 versus 4.21 +/- 0.6 versus 3.91 +/- 0.5 liters/min/m2). The 15-min VPL level was 1954.5 +/- 391/ng/ml and steady state levels at Hour 24 and 120 of the infusion were 468.1 +/- 59 and 422.8 +/- 52 ng/ml, respectively. Two of 11 treatment courses resulted in hypotension secondary to inordinately high 24-h levels of VPL (1233 and 1263 ng/ml). These two episodes required inotropic support but did not require the discontinuation of VPL. There were 8 of 11 partial responses, the majority of which consisted of peripheral cytoreduction of leukemic blasts and one M-2A response in AML. The levels of VPL achieved in this study have been shown to augment the in vitro cytotoxicity of vinblastine and VP-16 to resistant cell lines. Further clinical studies are needed to determined the maximal-tolerated dose of VPL in a Phase I study and to examine its efficacy in selected relapsed pediatric patients.
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PMID:Clinical trial of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. 253 92


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