Disease relevance of IMI 30

• The hematologic toxicity of 4-demethoxydaunorubicin (4-dmDNR), a new anthracycline more potent and less cardiotoxic than doxorubicin (Dx), was studied [1].
• The purpose of this study was to determine the relative merits of idarubicin and daunorubicin in acute myeloid leukemia (AML) therapy [2].
• Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia [3].
• The MiCK assay was used for dose-response analyses of the sensitivities to IDR, DNR, and MTA of leukemia cells from 4 other patients (2 ANLL and 2 ALL) [4].
• The other clinically studied analogue, idarubicin (4-demethoxydaunorubicin), has shown clinical activity in leukemias and in breast tumors also when given p.o. The properties of idarubicin may be related to electronic factors and to the extensive bioconversion to 13(S)-idarubicinol [5].

Psychiatry related information on IMI 30

• Our case has many characteristics in common with the second type of t-AML such as: exposure to topoisomerase II active agents (idarubicin (IDA), mitoxantrone (MITOX), etoposide (VP16)), M4 FAB subtype, a latency period of 39 months and absence of a preleukemic phase [6].

High impact information on IMI 30

• Second-generation analogs like epirubicin or idarubicin exhibit improvements in their therapeutic index, but the risk of inducing cardiomyopathy is not abated [7].
• The 10% inhibitory concentration (IC(10)) of idarubicin was 0.5 nM in MOLT4 and 1.5 nM in HL60 cells [8].
• The combination of idarubicin with vorinostat at 0.075 microM or VPA at 0.25 mM resulted in at least an additive loss of cell viability in both lines [8].
• The results of the Italian pediatric experience with the multicentric Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA)-Italian Pediatric Hematology and Oncology Group (AIEOP) "AIDA" (ATRA and idarubicin) trial are presented [9].
• Patients 60 years or older with APL who were enrolled in 2 successive multicenter PETHEMA studies received induction therapy with all-trans retinoic acid (ATRA) and idarubicin, consolidation with 3 anthracycline monochemotherapy courses with or without ATRA, and maintenance with ATRA and low-dose chemotherapy [10].

Chemical compound and disease context of IMI 30

• Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma [11].
• DLTs were HFS, rash, and mucositis on the troxacitabine plus idarubicin combination [12].
• Doxorubicin and idarubicin are very effective anticancer drugs in the treatment of human hematological malignancies and solid tumors [13].
• DNA sequence specificities of bisantrene, genistein, piroxantrone and ellipticinium were determined by using simian virus 40 DNA and compared to those of mitoxantrone, 4-demethoxydaunorubicin, VM-26 and mAMSA [14].
• A phase I trial of a single high dose of idarubicin combined with high-dose cytarabine as induction therapy in relapsed or refractory adult patients with acute lymphoblastic leukemia [15].

Biological context of IMI 30

• We show that prior incubation of human myeloid leukemic cells with ATRA or 1,25(OH)2 D3 induced resistance to idarubicin-induced apoptosis, which was modulated by coincubation with GM-CSF [16].
• We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content [17].
• As part of those studies, we have characterized the plasma pharmacokinetics of idarubicin and the major circulating metabolite idarubicinol in 21 patients [18].
• Enhanced sensitivity of the rat hepatoma cell to the daunorubicin analogue 4-demethoxydaunorubicin associated with induction of DNA damage [19].
• Inhibition of DNA synthesis by idarubicin parallels inhibition of cell growth; however, sensitivity of DNA synthesis to idarubicin is significantly less than that for cell proliferation (IC50 values of 0.5 microM and 0.025 microM, respectively) [19].

Anatomical context of IMI 30

• Prospective RT-PCR analyses were performed since 1993 at diagnosis and at preestablished time intervals during follow-up in bone marrow (BM) samples of 163 patients with PML/RARalpha+ APL enrolled in the multicenter Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) trial AIDA (All-trans retinoic acid plus Idarubicin) [20].
• There were 3 patients who also received idarubicin because of a white blood cell (WBC) count of more than 30 000/microL [21].
• DNA synthesis in mouse embryo fibroblasts stimulated by fetal calf serum was inhibited equally by the two compounds, although 4-Demethoxydaunorubicin was slightly more active than was daunorubicin when inhibiting RNA synthesis [22].
• Idarubicin was detected in 2 of 21 cerebrospinal fluid samples obtained 18-30 h after administration [18].
• Damage to the cell membrane or alterations in mitochondrial integrity do not appear to represent components of idarubicin toxicity in this tumor cell line [19].

Associations of IMI 30 with other chemical compounds

• We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy [23].
• Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7) [24].
• Compounds containing a daunosamine sugar moiety (Adriamycin, daunomycin, 4-demethoxydaunomycin, 4-demethoxyadriamycin, and carminomycin) were highly active in both mutagenesis assays [25].
• The interaction between three anthracycline antibiotics of second generation (9-deoxydoxorubicin, 9-DAM, 4-demethoxydaunorubicin, 4-DDM, 4'-deoxydoxorubicin, 4'-DAM) and DNA in the nucleosomal structure was investigated using fluorescence and circular dichroism techniques [26].
• The formation of semiquinone free radicals of doxorubicin, epirubicin, daunorubicin, and idarubicin was measured by electron paramagnetic resonance (EPR) spectroscopy in hypoxic suspensions of chinese hamster ovary (CHO) cells [27].

Gene context of IMI 30

• Pgp function was a prognostic factor in patients treated by daunorubicin and idarubicin but not by mitoxantrone [28].
• In contrast, BCRP expression was a prognostic factor in patients treated by daunorubicin and mitoxantrone but not by idarubicin [28].
• Anti-CD33 monoclonal antibodies enhance the cytotoxic effects of cytosine arabinoside and idarubicin on acute myeloid leukemia cells through similarities in their signaling pathways [29].
• To elucidate the role of DNA repair in this phenomenon we examined the capacity of murine BaF3 lymphoid cells and their TEL/ABL-transformed counterparts to repair DNA lesions caused by gamma- and UV-radiations and the anti-cancer drug, idarubicin [30].
• We investigated the effects of amifostine on idarubicin-induced DNA damage and repair in murine pro-B lymphoid BaF3 cells and BaF3-TEL/JAK2-transformed cells using alkaline single cell gel electrophoresis (comet assay) [31].

Analytical, diagnostic and therapeutic context of IMI 30

• Treatment consisted of ATRA and idarubicin induction followed by 3 polychemotherapy consolidation courses [9].
• Subsequently, however, overall (+/- idarubicin) rates of PCR positivity were 0/12 at 3 months, 1/10 at 6 months, 1/7 at 9 and 12 months, and 0/4 at 15 to 17 months [32].
• Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up [33].
• Phase I and clinical pharmacology studies of intravenous and oral administration of 4-demethoxydaunorubicin in patients with advanced cancer [34].
• Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia [35].

References