Effects of idarubicin: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Main Research Findings

Idarubicin is an anticancer drug used to treat a variety of cancers, including acute myeloid leukemia (AML) and breast cancer. 17 investigated the pharmacokinetics of orally administered idarubicin in 14 breast cancer patients. The study found that the half-life of idarubicin was 19 hours, and the half-life of idarubicinol, its active metabolite, was 60 hours. The study also found that the sum of the plasma AUCs was lower in patients with rapid progression than in patients who responded to treatment. 4 found that anti-CD33 monoclonal antibodies can enhance the cytotoxic effects of cytosine arabinoside and idarubicin on AML cells. 6 evaluated the safety, efficacy, and microenvironmental effects of idarubicin-loaded drug-eluting embolic transarterial chemoembolization in a rabbit liver tumor model. 8 found that the side effects of idarubicin are schedule-dependent in patients who have received T-cell depleted allogeneic bone marrow transplants. The study found that early administration of idarubicin was associated with less severe oral mucositis and faster bone marrow recovery. 5 demonstrated that an anti-CD19-idarubicin immunoconjugate resulted in complete tumor regression in an experimental model. 21 assessed the effects of intensive induction and consolidation chemotherapy with idarubicin and high-dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia (ALL). The study found that the intensive AML protocol resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes. 16 found that 1-methyl-3-propyl-7-butylxanthine (MPBX) enhanced the antitumor activity of idarubicin and reduced bone marrow suppression in P388 tumor-bearing mice. 9 compared the effects of idarubicin with other anthracyclines in patients with newly diagnosed leukemia. The study suggested that idarubicin may be the most effective and tolerable anthracycline. 12 found that 5-aza-2'-deoxycytidine combined with either amsacrine or idarubicin showed a significant complete remission rate in patients with relapsed acute leukemia. 13 demonstrated that P-glycoprotein (P-gp) inhibitors such as verapamil and PSC 833 can influence the myocardial uptake, metabolism, and effects of idarubicin. 18 found that 2-deoxy-D-glucose (2-DG) enhances the anti-cancer effects of idarubicin on idarubicin-resistant P388 leukemia cells. 19 reported a case where idarubicin was administered during pregnancy and the fetus showed no signs of cardiac failure but did show signs of transient myelosuppression, hepatopathy, and elevated creatine kinase. 11 investigated the cellular uptake and antiproliferative effects of idarubicin and daunorubicin in human leukemic cells. The study found that idarubicin is less vulnerable to MDR1-mediated transport than daunorubicin. 2 found that rapamycin and idarubicin have synergistic cytotoxic effects on human acute T-cell lymphoblastic leukemia Jurkat cells. 15 found that leukemia bone marrow stromal cells increase the resistance of HL-60 cells to idarubicin. 1 found that idarubicin induces apoptosis in HL-60 cells in a dose-dependent manner. 22 found that idarubicin and idarubicinol increased coronary vascular resistance in rats. The study suggested that these drugs may act through a common cellular mechanism. 7 demonstrated that idarubicin and idarubicinol have significant cytotoxic activity against multicellular spheroids. showed that doxorubicin and idarubicin have different cardiovascular effects in conscious rats. 14 found that idarubicin can cause acute neurohumoral activation and cardiovascular effects in leukemia patients. 10 found that several phenolic antioxidants, such as quercetin, rutin, naringenin, resveratrol, and trolox, can protect against idarubicin-induced DNA damage. 20 found that an aptamer targeting elongation factor 1A (eEF1A) impairs hepatocarcinoma cell viability and potentiates the effects of bortezomib and idarubicin. 3 compared the action of amifostine and melatonin on DNA-damaging effects and apoptosis induced by idarubicin. The study found that melatonin protected both normal and cancer cells against genotoxic treatment and apoptosis induced by idarubicin, while amifostine reduced apoptosis and DNA damage in normal cells, but it potentiated these effects in cancer cells.

Benefits and Risks

Benefit Summary

Idarubicin is an effective anticancer drug that can be used to treat a variety of cancers, including acute myeloid leukemia (AML) and breast cancer. Idarubicin may be more effective and tolerable than other anthracyclines, and it can also be used in combination with other anticancer drugs.

Risk Summary

Idarubicin can cause side effects such as cardiotoxicity, myelosuppression, and gastrointestinal problems. It can also affect the fetus if administered during pregnancy. Melatonin may protect against the DNA damage and apoptosis caused by idarubicin, but it should be used with caution in cancer therapy. Idarubicin can be reductively bioactivated by NADPH-cytochrome P450 reductase to generate free radicals that can cause DNA strand breaks, which may contribute to its genotoxic effects.

Comparison Across Studies

Commonalities

Idarubicin has been shown to be cytotoxic to a variety of cancer cells. Idarubicin can be used in combination with other anticancer drugs to enhance its effects. Idarubicin inhibits DNA synthesis in cancer cells, leading to cell death.

Differences

The effectiveness and side effects of idarubicin can vary depending on the method of administration, dosage, and co-administered drugs. The effectiveness of idarubicin can also vary depending on the type of cancer and the patient’s overall health.

Consistency and Contradictions of Findings

The findings from different studies on the effects of idarubicin vary. This variation is likely due to differences in study design, participant populations, and other factors. Although idarubicin can be combined with other anticancer drugs to enhance its effects, it can also enhance the risk of side effects. While melatonin may protect against DNA damage and apoptosis caused by idarubicin, it should be used with caution in cancer therapy. Idarubicin can cause DNA strand breaks, which may contribute to its genotoxic effects.

Real-World Application and Considerations

Idarubicin should be administered by a healthcare professional in a safe and appropriate manner. It’s important to be aware of the potential side effects of idarubicin, such as cardiotoxicity, myelosuppression, and gastrointestinal problems. It should not be used during pregnancy. Melatonin may be beneficial in protecting against the harmful effects of idarubicin, but its use should be discussed with a doctor. Idarubicin may cause DNA strand breaks, which may contribute to its genotoxic effects.

Limitations of Current Research

The research on idarubicin is still ongoing and more research is needed. The effects of idarubicin can vary between individuals, and more research is needed to understand the reasons for this variation. The effects of combining idarubicin with other anticancer drugs should be investigated further. It would be beneficial to develop methods to predict the effectiveness of idarubicin on an individual basis and methods to reduce the side effects of idarubicin. Additional research is needed to understand the mechanisms by which melatonin protects against the DNA damage and apoptosis caused by idarubicin and the mechanisms by which idarubicin causes DNA strand breaks. It’s also important to assess the genotoxic potential of idarubicin.

Future Research Directions

Future research on idarubicin should focus on the following areas. Further research is needed to fully understand the effects of idarubicin. The effects of combining idarubicin with other anticancer drugs should be investigated further. Methods to predict the effectiveness of idarubicin on an individual basis and methods to reduce the side effects of idarubicin should be developed. Further research is needed to understand the mechanisms by which melatonin protects against the DNA damage and apoptosis caused by idarubicin and the mechanisms by which idarubicin causes DNA strand breaks. The genotoxic potential of idarubicin should be evaluated.

Conclusion

Idarubicin is an effective anticancer drug that can be used to treat a variety of cancers. However, it is important to be aware of the potential side effects of idarubicin. It’s essential to discuss with your doctor about the potential benefits and risks of this drug. Further research is needed to understand the long-term effects of idarubicin and to develop safer and more effective treatments.

Literature analysis of 23 papers
Positive Content
17
Neutral Content
4
Negative Content
2
Article Type
1
1
1
1
23
1.

Dose dependent biological effects of idarubicin in HL-60 cells: alterations of the cell-cycle and apoptosis.

Author: MarekováM, VávrováJ, VokurkováD

TP-53 deficient cells of human leukaemia HL-60 were found to die by apoptosis after treatment with Idarubicin, with the rate of apoptosis dependent on the dose of Idarubicin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

[Synergistic cytotoxic effects of rapamycin and idarubicin on human acute T-cell lymphoblastic leukemia Jurkat cells].

Author: ZhaoYan-min, WuKang-ni, WangYing-jia, WuGong-qiang, CaoWei-jie, YuXiao-hong, HuangHe

Enhanced apoptosis
Synergistic anti-proliferative effect

Combining idarubicin (IDA) with the mTOR inhibitor rapamycin (Rapa) showed a synergistic effect in killing Jurkat cells, a human T-cell acute lymphoblastic leukemia cell line. The combination significantly increased apoptosis, inhibited mTOR signaling, and reduced ERK phosphorylation. This suggests that combining these drugs may be an effective treatment strategy for leukemia.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

3.

A comparison of the action of amifostine and melatonin on DNA-damaging effects and apoptosis induced by idarubicin in normal and cancer cells.

Author: MajsterekIreneusz, GlocEwa, BlasiakJanusz, ReiterRussel J

Cell protection
Potentiated apoptosis in cancer cells

Amifostine protected normal cells but potentiated DNA damage and apoptosis in cancer cells when used with idarubicin. Melatonin protected both normal and cancer cells from these effects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Anti-CD33 monoclonal antibodies enhance the cytotoxic effects of cytosine arabinoside and idarubicin on acute myeloid leukemia cells through similarities in their signaling pathways.

Author: BalaianLarisa, BallEdward D

AML cell growth inhibition

This study examined the potential for anti-CD33 monoclonal antibody (mAb) and chemotherapy agents (CA) to cooperate in inhibiting growth of primary AML samples and AML cell lines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

5.

Preclinical investigation of the antitumour effects of anti-CD19-idarubicin immunoconjugates.

Author: RowlandA J, PieterszG A, McKenzieI F

Cancer treatment
Reduced toxicity

Idarubicin conjugated to an anti-CD19 antibody showed selective cytotoxicity for CD19+ cells in an experimental model of acute lymphoblastic leukemia, resulting in complete tumor regression in some mice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Idarubicin-Loaded ONCOZENE Drug-Eluting Bead Chemoembolization in a Rabbit Liver Tumor Model: Investigating Safety, Therapeutic Efficacy, and Effects on Tumor Microenvironment.

Author: BordeTabea, Laage GauppFabian, GeschwindJean-Francois, SavicLynn J, MiszczukMilena, RexhaIrvin, AdamLucas, WalshJohn J, HuberSteffen, DuncanJames S, PetersDana C, SinusasAlbert, SchlachterTodd, GebauerBernhard, HyderFahmeed, ComanDaniel, van BreugelJohanna M M, ChapiroJulius

DEE chemoembolization
tumor acidosis
tumor devascularization
ischemia
toxicity

A rabbit liver tumor model was used to assess the efficacy and toxicity of idarubicin-loaded drug-eluting embolic (DEE) transarterial chemoembolization. Multiparametric MR imaging showed similar devascularization of embolized tumors for both 40-μm and 100-μm microspheres, but the smaller microsphere size was associated with greater toxicity. The findings suggest ischemia as the primary therapeutic mechanism.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Idarubicin and idarubicinol effects on breast cancer multicellular spheroids.

Author: OrlandiP, BarbaraC, BocciG, FioravantiA, Di PaoloA, Del TaccaM, DanesiR

Cancer treatment

This study investigates the in vitro cytotoxicity of idarubicin and its metabolite idarubicinol on MCF-7 breast cancer cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

The effects of idarubicin versus other anthracyclines for induction therapy of patients with newly diagnosed leukaemia.

Author: LiXi, XuShuangNian, TanYa, ChenJiePing

AML treatment

Idarubicin is a promising anthracycline for induction therapy of newly diagnosed acute myeloid leukemia (AML), although definitive evidence for its superiority over other anthracyclines is lacking.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

10.

Evaluation of the protective effects of quercetin, rutin, naringenin, resveratrol and trolox against idarubicin-induced DNA damage.

Author: CelikHaydar, ArinçEmel

Protection against DNA damage

Idarubicin, a synthetic anthracycline anticancer drug, can undergo reductive bioactivation by NADPH-cytochrome P450 reductase to form free radicals that cause DNA strand breaks. This study investigates the protective effects of several phenolic antioxidants against idarubicin's DNA-damaging effect.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).

Author: WillemzeR, SuciuS, ArchimbaudE, MuusP, StryckmansP, LouwagieE A, BernemanZ, TjeanM, WijermansP, DohnerH, JehnU, LabarB, JaksicB, DardenneM, ZittounR

Good antileukemic agent
Significant toxicity

A combination therapy with 5-Aza-2'-deoxycytidine and either amsacrine or idarubicin achieved a complete remission in 36.5% of patients with relapsed acute myeloid or lymphocytic leukemia. While effective, this treatment had prolonged digestive tract and hematologic toxicity. Further investigation is needed in previously untreated leukemia.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

15.

[Effects of leukemia bone marrow stromal cells on resistance of co-cultured HL-60 to idarubicin].

Author: ZhangXi, WangPing, ChenXing-Hua, LiuLin, PengXian-Gui, WangQing-Yu, KongPei-Yan, LiuHong, ZhangYi, GaoLei, ZhongYong-Ming

Chemotherapy resistance reduction

This study examines the role of hematopoietic microenvironment abnormalities in the development of minimal residual disease (MRD) in leukemia. The study found that leukemia bone marrow stromal cells contribute to the increased resistance of HL-60 cells to chemotherapeutic agents, suggesting a potential role for these cells in the development of MRD.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

17.

Pharmacokinetics of oral idarubicin in breast cancer patients with reference to antitumor activity and side effects.

Author: ElbaekK, EbbehøjE, JakobsenA, JuulP, RasmussenS N, BastholtL, DalmarkM, SteinessE

Leukocyte reduction

Idarubicin, a chemotherapy drug, showed no significant age-related differences in pharmacokinetics in patients with breast cancer. However, patients with rapid disease progression had lower plasma drug levels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Idarubicin administered during pregnancy: its effects on the fetus.

Author: MatsuoKoji, ShimoyaKoichiro, UedaShuji, WadaKazuko, KoyamaMasayasu, MurataYuji

Complete remission
Elevated creatine kinase
Hepatopaty
Myelosuppression

This case report describes a pregnant woman diagnosed with acute myeloblastic leukemia. The woman received chemotherapy during pregnancy, leading to premature delivery and complications in the newborn. Despite the challenges, the mother achieved complete remission, highlighting the complex considerations and potential outcomes of cancer treatment during pregnancy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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