Menzies Health Institute and School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
Menzies Health Institute and School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
Crit Rev Oncol Hematol. 2017 Nov;119:59-65. doi: 10.1016/j.critrevonc.2017.09.006. Epub 2017 Sep 18.
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.
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.
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.
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.
许多当前的抗癌化疗药物都存在显著的副作用，这导致了更具针对性的治疗方法的探索。这导致了 Aurora A 激酶抑制剂作为潜在的抗癌治疗方法的探索。alisertib（MLN8237）已被证明是一种有效的 Aurora A 激酶抑制剂，在其治疗家族中具有最高的安全性。alisertib 的 I/II/III 期临床试验已经进行并报告了有希望的疗效，但也有严重的副作用。本文试图评估 alisertib 在各种癌症表型中的临床效果，并描述报告的副作用。
alisertib 的临床数据从 Medline、CINAHL、PubMed 和 Cochrane 对照试验中心注册库中系统检索，并在纳入前分三个阶段进行质量、相关性和创新性分析。
共有 7 项研究符合纳入标准，共纳入 630 例患者。alisertib 在各种肿瘤中的“潜在”临床效果令人鼓舞，因为它改善了疾病进展时间、无进展生存期和疾病稳定时间。因此，其作为一种新型抗癌疗法的进一步研究是合理的。然而，该药物的给药与相当高比例的患者发生严重的血液学紊乱有关。
alisertib 给药的抗肿瘤作用在各种类型的恶性肿瘤中是有说服力的。报告的副作用虽然严重，但在许多情况下是可以控制的。当可能时，建议采用局部或更有针对性的给药途径，以避免药物系统性给药时的脱靶事件。
