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)

In a study of 11 adult patients with acute nonlymphocytic leukemia (ANLL), infusion therapy with high-dose VP-16 and intermediate-dose cytosine arabinoside was administered. Response was assessed with reference to bone marrow aspirations performed on days 1; 12, 13, or 14; and 21 of treatment. All 7 of the patients with ANLL in relapse achieved marrow hypoplasia, and 3 of them achieved complete response. LFTs were elevated in most patients but no evidence of hepatocellular necrosis was observed. It is concluded that the value of VP-16 in ANLL may have been underestimated in the past because of inadequate dosing.
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PMID:High-dose VP-16 with intermediate-dose cytosine arabinoside in the treatment of relapsed acute nonlymphocytic leukemia. 367 1

Due to unmanageable complications the results of high-dose chemotherapy for remission induction were significantly worse in a group of elderly patients with AML than for younger ones (greater than vs. less than 50 years: CRR 44% vs. 78%, p = less than 0.005). Hence, different induction schedules were studied for older patients with AML. A high response rate to low-dose cytosine-arabinoside (LD-CAR) was observed in myeloblastic and promyelocytic leukaemias, but the complete remission rate was low. Induction treatment with VP 16-213, aclacinomycin, cytosine-arabinoside and thioguanine resulted in a high complete remission rate (69%). Toxic side effects cannot be excluded in individual cases. These results justify prospective studies to evaluate the significance of the efficacy of these induction schedules.
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PMID:[Various induction therapies in older patients with acute myeloid leukemias]. 385 68

Thirteen patients with AML in first relapse were treated with high dose combination chemotherapy followed by cryopreserved autologous bone marrow transplantation (ABMT). The first four patients received the COATA-Roma regimen, consisting of CTX, VCR, CA, 6-TG and ADM; nine additional patients received the BAVC regimen consisting of BCNU, AMSA, VP-16 and CA. A median of 1.6 X 10(8) fractionated nucleated bone marrow cells/kg body weight were reinfused. The median of GM-CFU-C recovered was 4.7 X 10(4)/kg. Out of 13 patients, 10 (76.9%) achieved CR, 3 had profound aplasia and died from hemorrhagic or infectious complications. Of the 10 patients who achieved CR, 1 died after 1 week from heart failure, 5 relapsed respectively 17, 20, 21, 21, 42, weeks after ABMT, 4 are still in CR after 2+, 14+, 17+, and 120+, weeks. Of the 9 patients treated with BAVC regimen, 8(88.8%) achieved CR. Four patients relapsed after a median of 19.7 weeks and 4 are still in complete remission. Of interest is the fact that the second complete remission of one patient is longer than the first one, despite the fact that marrow was not purified by any in vitro treatment. In conclusion we can say that BAVC regimen is highly effective in obtaining second complete remission in patients with AML and prolonged disease free survival can be achieved at least in a small number of cases.
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PMID:Cryopreserved autologous bone marrow infusion following high dose chemotherapy in patients with acute myeloblastic leukemia in first relapse. 388 7

In a phase I/II study the tolerable doses and antileukemic efficacy of the combination AMSA and etoposide (VP 16-213) was assessed in 20 patients with refractory acute myeloid leukemia. The following 5 day treatment course was found tolerable and effective: AMSA 210 mg/m2/die on days 2, 3 and 4, and etoposide on days 1 and 5 as a 1 h infusion of 100 mg/m2 followed by a 23-h continuous infusion of 230 mg/m2. In 5 of 20 patients partial remissions were achieved; 4 of these patients were primarily resistant against two TAD induction cycles. Bone marrow aplasia without a residual blast population was achieved in 7 of the 8 patients with primary TAD resistance. AMSA/etoposide thus seems to express an antileukemic efficacy without cross-resistance against TAD.
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PMID:[AMSA/etoposide (VP 16-213). A phase I/II study in refractory acute myeloid leukemia]. 389

A Phase II clinical trial of NK 171 (Etoposide), a semisynthetic podophyllotoxin, was undertaken in 56 patients with advanced malignant lymphoma and 36 patients with acute leukemia. The dosage of NK 171 was 110-130 mg/m2 day p.o. or 80-100 mg/m2 day i.v. for 5 consecutive days. Of the 92 patients, 23.9% obtained a complete or partial remission. By tumor type, good responses were obtained in non-Hodgkin's lymphoma (34%, 17/50), Hodgkin's disease (25%, 1/4), AML (21.4%, 3/14), and CML-BC (25%, 1/4). Side effects included leukopenia (78.4%), alopecia (62.0%), anorexia (40.2%), nausea (30.4%) thrombocytopenia (25.6%) and fever (16.3%). These results demonstrated NK 171 to be an effective agent against malignant lymphoma and acute myeloblastic leukemia.
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PMID:[Phase II study of NK 171 (etoposide) on malignant lymphomas and acute leukemia. A cooperative study group on NK 171 in hematological malignancies]. 395 73

Thirty-eight children and young adults with advanced acute nonlymphocytic leukemia (ANLL) in relapse were treated with VP-16-213 plus azacitidine (5AZ). Each patient had previously received many chemotherapeutic drugs, including anthracyclines and cytarabine. Initially, 16 patients received a 5-day course of VP-16-213 (100 mg/m(2)) daily x 3 days and 5AZ 9150 mg/m(2)) daily x 2 days, repeated after 9-16 days. Since this treatment produced marrow hypoplasia and complete remission (CR) in only one of 16 patients, a more intensive regimen was devised: the remaining 22 patients received a course of VP-16-213 (200 mg/m(2)) daily x 3 days, followed by 5AZ (300 mg/Fm(2)) daily x 2 days, repeated after 1-2 days until the bone marrow became hypoplastic. After two to four courses, 18 patients had marrow hypoplasia and ten of these achieved CR. The proportion of patients achieving CR with the higher doses was significantly greater than that with the initial doses )P less than or equal to 0.05). The toxicity also increased with the higher doses, with major problems due to prolonged pancytopenia. Supportive therapy was required for severe bleeding and infections. We conclude that the intensive treatment with VP-16-213 plus 5AZ can effectively induce remission in patients with refractory advanced acute nonlymphocytic leukemia.
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PMID:Effective remission induction of refractory childhood acute nonlymphocytic leukemia by VP-16-213 plus azacitidine. 617 Apr 31

A study of children in relapse with acute nonlymphocytic leukemia (ANLL) previously maintained in remission with combination chemotherapy including cytosine arabinoside (Ara-C) was undertaken by Children's Cancer Study Group (CCSG) to assess the efficacy of cyclocytidine (Cyclo-C), a depot Ara-C, compared to parenteral Ara-C given every 12 hr. The reinduction protocol consisted of daunomycin combined with either Ara-C (Regimen 1) or Cyclo-C (Regimen 2). One-hundred thirty eligible patients were entered on the randomized study. Hematologic toxicity was significant in both regimens and resulted in four drug-related deaths. Cardiac toxicity was observed in five patients, manifested only by abnormal echocardiogram or electrocardiogram patterns in three and congestive heart failure in two patients. Seventy-seven of 112 evaluable patients achieved M-1 or M-2A marrow remissions (69%): 46 of 60 on Regimen 1 (75%), 30 of 52 on Regimen 2 (60%). The remission rate between the two regimens was not significantly different. There was no significant difference in the duration of remission comparing maintenance cyclophosphamide combined with Ara-C or with Cyclo-C. Addition of VP-16 and CCNU to the maintenance therapy did not prolong the duration of remission. This study indicates that patients with childhood ANLL previously treated with Ara-C and daunomycin can obtain a successful second remission. A single daily subcutaneous dose of Cyclo-C was found to be as efficacious as Ara-C given intravenously every 12 hr. The single dose schedule provides a convenient way to treat patients with relapsed ANLL in the outpatient setting.
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PMID:Evaluation of cyclocytidine in reinduction and maintenance therapy of children with acute nonlymphocytic leukemia previously treated with cytosine arabinoside: a report from Children's Cancer Study Group. 620 68

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

In a phase I study the combination of AMSA and etoposide was applied to 12 patients with intensively pretreated, refractory AML to evaluate the basis for a subsequent phase II study in terms of drug dosage and timing. Each treatment cycle consisted in a 5-day regimen of AMSA 210 mg/m2/d days 2, 3 and 4. Etoposide was administered on days 1 and 5 with a constant loading dose of 100 mg/m2 by an 1-h infusion followed by a 23-h infusion, the dose of which was escalated in 3 steps from 110 mg/m2 to 200 mg/m2 and 230 mg/m2. In 18 treatment cycles the recommended dosage for a subsequent phase II study was found to be 660 mg/m2 etoposide per cycle together with 630 mg/m2 AMSA per course. Main side effects were nausea and vomiting as well as mucositis; 1 patient developed a severe intrahepatic cholestasis. In 11 from 16 evaluable treatment cycles a significant reduction of bone marrow blasts was observed with a mean cytoreduction rate of 0,26 log10/d. 4 patients, 3 of whom were primarily resistent to 2 TAD induction courses, achieved a partial remission.
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PMID:[Combined therapy with AMSA and etoposide (VP 16-213) in refractory acute myeloid leukemia. A phase I study]. 638 64

A clinical study of a new semisynthetic podophyllotoxin etoposide (NK 171) was performed in patients with various hematological malignancies refractory to standard chemotherapies. The drug was given intravenously in a dose of 100-130 mg/m2/day for five days or orally in a dose of 130-170 mg/m2/day for five days. Out of 9 patients with non-Hodgkin's lymphoma, 2 CR and 4 PR were obtained; out of 4 acute nonlymphoblastic leukemias, 1 CR, and out of 4 chronic myerogenous leukemias 2 CR and 1 PR, were obtained. The dose limiting factor was leukopenia, and alopecia was frequent while other hematologic and gastrointestinal toxicities were mild. Etoposide (NK 171) had no clinical cross resistance to other antitumor agents, thus warranting further clinical trials, in combination chemotherapy against NHL, ANLL and CML-BC.
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PMID:[Phase II study of etoposide (NK 171) in advanced hematological malignancies]. 647 35


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