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)

Over the past 15 years, daunorubicin, cytosine arabinoside and, to a lesser extent, 6-thioguanine and etoposide have become the standard agents used to treat patients with acute myelogenous leukemia (AML). These agents have been used in various combinations and schedules with only small improvements in overall outcome because few other agents with promise were available. This situation has changed over the past few years so that today there are a number of new agents that have the potential to supplement or replace the standard drugs. Idarubicin, mitoxantrone, amsacrine, homoharringtonine, 2-chlorodeoxyadenosine, fludarabine, carboplatin, retinoids, colony stimulating factors, and interleukin-2 are discussed.
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PMID:New agents for treatment of children with acute myelogenous leukemia. 762 Sep 21

Idarubicin (IDA,4-demethoxydaunorubicin) is a new antineoplastic agent that is structurally related to daunorubicin (DNR) and has the same mechanism of action as DNR and doxorubicin (ADR). Unlike the other currently available anthracyclines, IDA has significant oral bioavailability (about 30%). Animal tumor studies have shown that it has greater antitumor activity at lower drug concentration than DNR. IDA is an effective agent for the management of acute myelogenous leukemia (AML). It has achieved greater response rates than the standard anthracycline, DNR, when it is administered with cytarabine in newly diagnosed patients. IDA is also an effective agent in acute lymphoblastic leukemia, lymphomas, breast cancer and some other tumors. Adverse effects are similar to those seen with other anthracyclines, although IDA may be associated with less cardiotoxicity than ADR or DNR.
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PMID:[Clinical pharmacology of idarubicin]. 830 77

An early phase II study of Idarubicin was performed in patients with acute leukemia. The dosages administered were 10 mg/m2, 12 mg/m2, or 15 mg/m2 by iv bolus, once daily for 3 consecutive days. The treatment was given to 47 patients who were in relapse or whose diseases had been refractory to remission induction therapy. Of the 47 patients, 35 were evaluable for response. The patients who showed a response (complete or partial remission) were 9 of 14 patients (64.3%) in the 10 mg/m2 group, 1 of 12 patients (8.3%) in the 12 mg/m2 group, and 3 of 9 patients (33.3%) in the 15 mg/m2 group, respectively. Remissions were achieved in 10 of 23 (43.5%) patients with acute myelogenous leukemia, and in 3 of 6 (50.0%) of those with chronic myelogenous leukemia in blast crisis. However, no remission was achieved in 6 patients with acute lymphocytic leukemia. As for patients who had received prior anthracycline therapy, remissions were achieved in 11 of 29 patients (37.9%), and so clinical cross resistance between idarubicin and other anthracyclines was thought to be partial. The principal adverse effects were gastrointestinal symptoms, alopecia, fever and infection. In the 15 mg/m2 group, there was an increased number of adverse events of WHO's grade 3 or over. The result indicated that Idarubicin is a useful drug for the treatment of acute leukemia, and the clinical optimal dosage estimated was either 10 mg/m2 or 12 mg/m2 once daily for 3 consecutive days.
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PMID:[Early phase II study of Idarubicin, a new anthracycline anticancer drug, in acute leukemia. Idarubicin Study Group]. 848 96

An early phase II study of a combination regimen consisting of Idarubicin and Cytarabine was performed in patients with acute myelogenous leukemia. Idarubicin at a dose of 10 mg/m2 or 12 mg/m2 was given by 5-min. iv bolus, once daily for 3 consecutive days and Cytarabine at a dose of 80 mg/m2 was given by 2-hour iv infusion, twice daily for 7 consecutive days. Of 19 patients treated, 17 were evaluable for responses. The patients who showed a response (complete or partial remission) were 4 of 10 (40.0%) in the 10 mg/m2 group, 6 of 7 (85.7%) in the 12 mg/m2 group, and in total, 10 of 17 patients (58.8%), respectively. Analysing relationship between prior chemotherapy and responses, all of 3 patients without pretreatment, 6 of 10 patients (60.0%) in the first relapse, and 1 of 4 patients (25.0%) whose disease had been refractory to induction therapy after relapse responded. Seven of 14 patients (50%) who had received prior anthracycline therapy, showed a response. The principal adverse effects were gastrointestinal symptoms, alopecia, fever and infection, similarly to those observed in Idarubicin single therapy. When combined with Cytarabine, Idarubicin increased the incidence and severity of gastrointestinal symptoms. Considering effectiveness and safety, the clinical optimal dosage of Idarubicin when used concomitantly with Cytarabine was judged to be 12 mg/m2 once daily for 3 consecutive days.
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PMID:[Early phase II study of Idarubicin combined with cytarabine in acute myelogenous leukemia. Idarubicin Study Group]. 848 97

We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo acute myeloid leukemia (AML) at the initial diagnosis in order to further define the relationship between the presence of P-gp on leukemic cells and the efficacy of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, induction and survival. We found that 30 (60%) of the 50 patients were negative for P-gp expression (group 1) and 20 patients (40%) were positive (group 2) for P-gp expression by MRK16MoAb using a cut of 10% positive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2 (p < 0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p < 0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No significant difference has been achieved in group 1 terms of median duration of overall survival between DNR and IDR regimen; on the contrary the median duration of OS in patients of group 2 treated with IDR regimen was significantly longer than DNR regimen (p < 0.005). These results confirm the prognostic value of P-gp expression in AML at diagnosis and we suggest that Idarubicin could be a valid anthracycline drug for reversing multidrug resistance.
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PMID:Anthracycline drugs and MDR expression in human leukemia. 886 11

A patient with acute monoblastic leukemia (AML, M5A) was treated successfully in December 1987. In 1993 after 6 years in complete remission, she presented with an intracutaneous nodular mass on her right upper arm which was resected in toto and shown to be undifferentiated monoblastic leukemia. Two further chloroma lesions were excised in July 1994 and March 1995 respectively. Bone marrow cytology and histology always showed a continuing complete remission with no evidence of leukemia relapse. In July 1995 she presented with a disseminated skin infiltrate and a relapse with 80% monoblasts in the bone marrow. After one course of chemotherapy (Idarubicin/Ara-C), a second complete remission was achieved and her leukemic skin infiltrate disappeared completely. This case illustrates that chloromas of the skin can occur as late as 6 years after treatment for AML and also emphasizes that the occurrence of a chloroma does not necessarily mean immediate leukemia relapse. It also stresses that a second complete remission can be achieved with standard AML-induction therapy despite widespread leukemic skin infiltrates in such patients.
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PMID:Cutaneous monoblastic leukemia as a first sign of relapse six years after autologous bone marrow transplantation for acute leukemia. 888 69

The GOELAM group conducted 2 consecutive trials on the treatment of de novo acute myeloblastic leukemia (AML) in adults. In the GOELAM1 protocol 786 patients aged 15-65 were randomized between two induction treatments (ARA-C 200 mg/m2/day for 7 days plus either Idarubicin 8 mg/m2/day for 5 days or Rubidazone 200 mg/m2/day for 4 days). Out of 731 evaluable patients, 521 (71%) achieved complete remission (CR) without significant difference between the 2 anthracyclines. For patients aged 51-65, the CR rate was significantly higher with Idarubicin (75%) than with Rubidazone (61%) (p = 0.03). In this group of patients the post-remission therapy consisted in only one course of high dose ARA-C plus m-Amsa and the 6 year disease free survival (DFS) was 24% (intention to treat analysis). For patients aged 15-50 years, the post remission therapy was either allogeneic bone marrow transplantation (BMT) (patients up to 40 years of age with an HLA identical sibling) or a first course of intensive consolidation chemotherapy (ICC) followed by a randomization between autologous unpurged bone marrow transplantation (ABMT) and a second course of ICC. There was no significant difference in the 4 year DFS between allogeneic BMT (42%) and the other types of intensive post remission-therapy (40%). The 4 year DFS was 42% for ABMT and 38% for ICC (p = 0.46) (intention to treat analysis). However the median duration of thrombocytopenia was much longer after ABMT (109.5 days versus 18.5 days p = 0.0001). The GOELAM SA3 randomized placebo-controlled protocol tested the impact of GM-CSF given during and after induction treatment for elderly patients (55-75 years). In this study, 232 evaluable patients received induction chemotherapy (Idarubicin 8 mg/m2/day for 5 days plus ARA-C 100 mg/m2/day for 7 days) plus placebo or GM-CSF 5 micrograms/kg/day from day 1 until the end of neutropenia. The CR rate was 61.5%. The median duration of neutropenia was shorter in the GM-CSF arm (22 days versus 27 days p = 0.0001). There was no overall significant advantage for the GM-CSF arm, in terms of CR rate and survival. However for patients age 55-64 the 2 year DFS was significantly higher in the GM-CSF arm (43% vs 17% p = 0.0013).
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PMID:Treatment of acute myeloblastic leukemia in adults. The GOELAM experience. 891 68

Sixty-one adult patients with relapsed or refractory acute myelogenous leukemia (AML) were treated in a cooperative study with Idarubicin 12 mg/m2/day on days 1 to 3 and AraC 1 g/m2/12h on days 1 to 4. Responding patients were scheduled for consolidation with Ida-IDAraC and bone marrow transplantation (BMT) when feasible. Twelve of 23 refractory patients (52%) and 21 of 38 relapsed patients (55%) achieved complete remission (CR). Refractory patients treated very early with Ida-IDAraC (CR 63%) and relapsed patients with initial CR > 6 months (CR 68%) were the subgroups with better CR rate. The only factor influencing the disease free survival (DFS) was the intensity of postremission therapy: Nine patients had severe toxicity with the salvage regimen and were excluded for consolidation, fourteen patients received Ida-IDAraC and ten patients proceeded to myelo-ablative therapy supported with autologous or allogeneic BMT. The three groups had different median DFS of 6 months, 9 months and 15 months respectively (P = 0.017). In summary, Ida-AraC is an efficient salvage regimen for AML. The CR rate seems to be improved in refractory patients if used promptly, but the long term outcome appears to depend on the intensity of treatment given once remission is achieved and on the ability to perform BMT.
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PMID:Idarubicin and intermediate dose ARA-C followed by consolidation chemotherapy or bone marrow transplantation in relapsed or refractory acute myeloid leukemia. 916 46

The current situation and perspectives for the treatment of acute myelogenous leukemia in adults were summarized. Due to the recent progress of chemotherapy, the complete remission (CR) rate is close to 80% in adults with newly diagnosed acute myelogenous leukemia in Japan. On the other hand, the long-term disease-free survival rate is 30-40% in CR cases. The allogeneic bone marrow transplantation (allo BMT) during the first CR has a low relapse rate compared with that of chemo therapy. However, the therapy-related mortality is not inconsiderable, so, the time of allo BMT is controversial. Idarubicin has a superior CR rate as well as long-term disease-free survival in comparison with daunorubicin, and it is becoming the first line treatment for acute myelogenous leukemia in adults.
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PMID:[Current situation and perspective for treatment of acute myelogenous leukemia in adults]. 949 19

A 9-year old boy was admitted to our hospital due to a relapse of acute myelogenous leukemia (AML). A chromosomal analysis at the time of relapse revealed abnormalities in addition to 45, X,-Y, t(8;21) (q22;q22) when AML was first diagnosed. The patient was given granulocyte-colony stimulating factor (G-CSF), cytosine arabinoside (Ara-C) and aclarubicin (CAG therapy), but this treatment regimen was not effective. He was next treated with G-CSF (started 3 days prior to the administration of anticancer drugs), Ara-C, (200 mg/mm2 for 7 days), Etoposide (VP.16, 150 mg/mm2 for 5 days) and Idarubicin (8 mg/mm2 for 5 days) according to the modified Japan Cooperative Protocol ANLL 91 for children. Although his condition had been septic and he had experienced renal and respiratory failure, he achieved a complete remission after 140 days without additional therapy. The patient returned to a condition of health and received a bone marrow transplant from an unrelated donor. We concluded that this treatment regimen is effective for the relapse of AML in children.
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PMID:[Successful treatment with idarubicin in a pediatric case of t(8;21) acute myelogenous leukemia with additional chromosomal abnormalities at relapse]. 975 Apr 57


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