ArticleInvestigational new drugs2015
Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose.
Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inter-ethnic differences in pharmacokinetics-is there more that unites than divides?Pharmacology research & perspectives · 2021Pooled it
- Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.Clinical and translational science · 2021Trial
- Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Ginsenoside Rh2 inhibits non-small-cell lung cancer malignant progression through targeting AURKA.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- Article
- Asia-Inclusive Clinical Research and Development Enabled by Translational Science and Quantitative Clinical Pharmacology: Toward a Culture That Challenges the Status Quo.Clinical pharmacology and therapeutics · 2023Article
- Treatment of extranodal NK/T-cell lymphoma: From past to future.Frontiers in immunology · 2023Review
- Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- How we treat NK/T-cell lymphomas.Journal of hematology & oncology · 2022Review
- Review
- Identification of Selective CYP3A7 and CYP3A4 Substrates and Inhibitors Using a High-Throughput Screening Platform.Frontiers in pharmacology · 2022Article
- Article
- The role of Aurora-A in human cancers and future therapeutics.American journal of cancer research · 2020Review
- Mass balance, routes of excretion, and pharmacokinetics of investigational oral [Investigational new drugs · 2019Article
- Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Novel findings from the Asian Lymphoma Study Group: focus on T and NK-cell lymphomas.International journal of hematology · 2018Review
- Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.British journal of clinical pharmacology · 2018Article
- Article
- Continuous anti-angiogenic therapy after tumor progression in patients with recurrent high-grade epithelial ovarian cancer: phase I trial experience.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis phase 1 study assessed the pharmacokinetics (PK), maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety, and preliminary efficacy of the investigational Aurora A kinase inhibitor, alisertib, in East Asian patients with advanced solid tumors or lymphomas. PATIENTS AND
methodsPatients received alisertib twice-daily (BID) for 7 days in 21-day cycles. Doses were escalated (3 + 3) from 30 mg BID based on cycle 1 dose-limiting toxicities (DLTs) until the MTD, followed by expansion for PK/safety characterization.
resultsThirty-six patients (61 % Chinese, 36 % Korean, 3 % Malay) received alisertib (30 mg BID, n = 30; 40 mg BID, n = 6; median, 2.5 cycles). Alisertib exposures increased approximately dose proportionally, and mean half-life was 16 h. Geometric mean apparent oral clearance (2.65 L/h) was 40 % lower than previous estimates in Western patients, resulting in approximately 70 % higher mean dose-normalized, steady-state exposures (735 nM*h/mg) in East Asian patients. Two patients experienced DLTs at 40 mg BID (grade 3 stomatitis; grade 4 neutropenia); the MTD/RP2D was 30 mg BID. Common toxicities (grade ≥3 at RP2D) were neutropenia (50 %), diarrhea (13 %), and stomatitis (10 %). One patient with extranodal T-/NK-cell lymphoma (nasal type) achieved a partial response and 18 (51 %) had stable disease.
conclusionThe MTD/RP2D of alisertib in East Asian patients (30 mg BID) was lower than in Western patients (50 mg BID), consistent with higher systemic exposures in the East Asian population. Alisertib was generally well tolerated and showed signs of antitumor activity in East Asian cancer patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.