***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Previously , we and others showed that hypoxia‐inducible factor‐1α ( HIF‐1α ) and transcriptionally upregulated Aurora‐A were required for disease progression in several tumors . Here , we address the clinicopathologic value of Aurora‐A and HIF‐1α in locally advanced nasopharyngeal carcinoma ( NPC ) . Aurora‐A and HIF‐1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a r and omized controlled trial . Of these patients , 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy  , and acted as the training set , and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy  were used as the testing set to vali date the prognostic effect of Aurora‐A and HIF‐1α . We found that Aurora‐A and HIF‐1α were highly expressed in NPC , but were deficient in normal adjacent epithelia . In the testing set , Aurora‐A overexpression predicted a shortened 5‐year overall survival ( 59.1 % vs 82.5 % , P = 0.024 ) , progression‐free survival ( 44.8 % vs 79.8 % , P = 0.004 ) , and distant metastasis‐free survival ( 43.0 % vs 17.3 % , P = 0.016 ) . Multivariate regression analysis confirmed that Aurora‐A was indeed an independent prognostic factor for death , recurrence , and distant metastasis both in the testing set and overall patients . Moreover , a positive correlation between Aurora‐A and HIF‐1α was detected ( P = 0.037 ) . Importantly , although HIF‐1α did not show any prognostic effect for patient outcome , the subset with Aurora‐A and HIF‐1α co‐overexpression had the poorest overall , progression‐free , and distant metastasis‐free survival ( all P < 0.05 ) . Our results confirmed that Aurora‐A was an independent prognostic factor for NPC . Aurora‐A combined with HIF‐1α refined the risk definition of the patient subset , thus potentially directing locally advanced NPC patients for more selective therapy . ( Cancer Sci , doi : 10.1111/j.1349‐7006.2012.02332.x , 2012 OBJECTIVES Aurora A kinase ( AAK ) , a key mitotic regulator , is implicated in the pathogenesis of several tumors , including ovarian cancer . This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 ( alisertib ) , in patients with platinum-refractory or -resistant epithelial ovarian , fallopian tube , or primary peritoneal carcinoma . METHODS Adult women with malignant , platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days ' rest ( 21-day cycles ) . The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors ( RECIST ) and /or CA-125 criteria . Secondary endpoints included response duration , clinical benefit rate , progression-free survival ( PFS ) , time-to-progression ( TTP ) , and safety . RESULTS Thirty-one patients with epithelial ovarian ( n=25 ) , primary peritoneal ( n=5 ) , and fallopian tube carcinomas ( n=1 ) were enrolled . Responses of 6.9 - 11.1 month duration were observed in 3 ( 10 % ) patients with platinum-resistant ovarian cancer . Sixteen ( 52 % ) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥3 months in 6 ( 19 % ) . Median PFS and TTP were 1.9 months . Most common drug-related grade ≥3 adverse events were neutropenia ( 42 % ) , leukopenia ( 23 % ) , stomatitis , and thrombocytopenia ( each 19 % ) ; 6 % reported febrile neutropenia . CONCLUSIONS These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer . MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer Purpose : This phase I study evaluated the safety , pharmacokinetics , pharmacodynamics , and efficacy of the investigational oral drug MLN8237 ( alisertib ) , a small-molecule Aurora A kinase ( AAK ) inhibitor , in 87 adult patients with advanced solid tumors . Experimental Design : Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7 , 14 , or 21 days , followed by 14 days ' rest per cycle . MLN8237 pharmacokinetics was characterized , and the relative bioavailability of an enteric-coated tablet ( ECT ) formulation was evaluated in reference to the original powder-in-capsule ( PIC ) formulation . Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies . Tolerability and response to treatment were assessed . Results : Common toxicities included fatigue , nausea , and neutropenia . Plasma exposures increased dose proportionally ( 5–150 mg/d ) , and were similar for PIC and ECT . The terminal half-life was 23 hours . At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule , the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7 , a finding consistent with AAK inhibition . One ( 1 % ) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles ; 20 ( 23 % ) patients achieved stable disease for ≥3 months . Conclusions : This first-in-human trial of MLN8237  showed tolerability and favorable pharmacokinetics in this patient population . The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles , which is being evaluated further in the treatment of various solid tumors and hematologic malignancies . Clin Cancer Res ; 18(17 ) ; 4775–84 . © 2012 AACR BACKGROUND Alisertib is an investigational , oral , selective inhibitor of aurora kinase A. We aim ed to investigate the safety and activity of single-agent alisertib in patients with predefined types of advanced solid tumours . METHODS We did a multicentre phase 1/2 study at 40 centres in four countries ( Czech Republic , France , Pol and , and the USA ) . Here , we report results from phase 2 ; enrolment for the study began on Feb 16 , 2010 , and ended on May 3 , 2013 . Adult patients were eligible for the study if they had either breast cancer , small-cell lung cancer , non-small-cell lung cancer , head and neck squamous-cell carcinoma , or gastro-oesophageal adenocarcinoma that had relapsed or was refractory to chemotherapy . Patients had to have undergone two or fewer previous cytotoxic regimens ( four or fewer for breast cancer patients ) , not including adjuvant or neoadjuvant treatments . Enrolment followed a two-stage design : to proceed to the second stage , two or more objective responses were needed in the first 20 response-assessable patients in each of the five tumour cohorts . Alisertib was administered orally in 21-day cycles at the recommended phase 2 dose of 50 mg twice daily for 7 days followed by a break of 14 days . The protocol -specified primary endpoint was the proportion of patients with an objective response , assessed by Response Evaluation Criteria In Solid Tumors version 1.1 in the response-assessable population ( ie , patients with measurable disease who received at least one dose of alisertib and had undergone at least one post-baseline tumour assessment ) . This completed trial is registered with Clinical Trials.gov , NCT01045421 . FINDINGS By May 31 , 2013 , 249 patients had been treated , 53 with breast cancer , 60 with small-cell lung cancer , 26 with non-small-cell lung cancer , 55 with head and neck squamous-cell carcinoma , and 55 with gastro-oesophageal adenocarcinoma . Among response-assessable patients , an objective response was noted in nine ( 18 % , 95 % CI 9 - 32 ) of 49 women with breast cancer , ten ( 21 % , 10 - 35 ) of 48 participants with small-cell lung cancer , one ( 4 % , 0 - 22 ) of 23 patients with non-small-cell lung cancer , four ( 9 % , 2 - 21 ) of 45 people with head and neck squamous-cell carcinoma , and four ( 9 % , 2 - 20 ) of 47 individuals with gastro-oesophageal adenocarcinoma ; all were partial responses . Adverse events were similar across tumour types . The most frequent drug-related grade 3 - 4 adverse events included neutropenia ( n=107 [ 43 % ] ) , leukopenia ( 53 [ 21 % ] ) , and anaemia ( 26 [ 10 % ] ) . Serious drug-related adverse events were reported in 108 ( 43 % ) patients . INTERPRETATION These data support further clinical assessment of alisertib in patients with solid tumours , particularly those with breast cancer and small-cell lung cancer . FUNDING Millennium Pharmaceuticals , Inc , a wholly owned subsidiary of Takeda Pharmaceutical Company Limited 
    Output:
    
Our present meta- analysis indicates that the Aurora kinase A is an effective prognosticator in solid tumors patients .