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  • Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data

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    Author(s)
    Tayyar, Yaman
    Jubair, Luqman
    Fallaha, Sora
    McMillan, Nigel AJ
    Griffith University Author(s)
    McMillan, Nigel
    Tayyar, Yaman
    Year published
    2017
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    Abstract
    Background: Many current anticancer chemotherapeutics suffer from significant side effects, which have led to the exploration of more targeted therapies. This resulted in the exploration of inhibitors of Aurora A kinase as a potential anti-cancer treatment. Alisertib (MLN8237) has proven to be a potent Aurora A kinase inhibitor that had the highest safety profile among its therapeutic family. Phase I/II/III clinical trials with Alisertib have been carried out and reported promising efficacy, yet serious side effects. This article attempts to assess the clinical effect of Alisertib administration in various cancer phenotypes ...
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    Background: Many current anticancer chemotherapeutics suffer from significant side effects, which have led to the exploration of more targeted therapies. This resulted in the exploration of inhibitors of Aurora A kinase as a potential anti-cancer treatment. Alisertib (MLN8237) has proven to be a potent Aurora A kinase inhibitor that had the highest safety profile among its therapeutic family. Phase I/II/III clinical trials with Alisertib have been carried out and reported promising efficacy, yet serious side effects. This article attempts to assess the clinical effect of Alisertib administration in various cancer phenotypes while describing the reported side effects. Methods: Alisertib clinical data were systematically retrieved from Medline, CINAHL, PubMed, and Cochrane Central Register of Controlled Trials and analyzed for quality, relevance, and originality in three stages prior to inclusion. Results: Overall, seven studies met inclusion criteria and enrolled a total of 630 patients. The reported “potential” clinical effect of Alisertib in various tumours is promising as it improved time to disease progression, progression-free survival, and the duration of disease stability. The achieved improvement therefore rationalizes its further investigation as a novel anticancer therapy. However, the administration of the drug was associated with serious haematological disturbances in a relatively high percentage of patients. Conclusion: The evidence of the anti-tumour effect of Alisertib administration is compelling in various types of malignancies. The reported side effects were serious but manageable in many cases. Topical or more targeted routes of administration are suggested when possible to overcome off-target events with systematic administration of the drug.
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    Journal Title
    Critical Reviews in Oncology/Hematology
    Volume
    119
    DOI
    https://doi.org/10.1016/j.critrevonc.2017.09.006
    Copyright Statement
    © 2017 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Cardiovascular medicine and haematology
    Chemotherapy
    Oncology and carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/373198
    Collection
    • Journal articles

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