Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Venkatakrishnan, K[Venkatakrishnan, Karthik] | - |
dc.contributor.author | Kim, TM[Kim, Tae Min] | - |
dc.contributor.author | Lin, CC[Lin, Chia-Chi] | - |
dc.contributor.author | Thye, LS[Thye, Lim Soon] | - |
dc.contributor.author | Chng, WJ[Chng, Wee Joo] | - |
dc.contributor.author | Ma, B[Ma, Brigette] | - |
dc.contributor.author | Chen, MH[Chen, Ming Huang] | - |
dc.contributor.author | Zhou, XF[Zhou, Xiaofei] | - |
dc.contributor.author | Liu, H[Liu, Hua] | - |
dc.contributor.author | Kelly, V[Kelly, Virginia] | - |
dc.contributor.author | Kim, WS[Kim, Won Seog] | - |
dc.date.accessioned | 2021-08-02T04:07:47Z | - |
dc.date.available | 2021-08-02T04:07:47Z | - |
dc.date.created | 2016-08-07 | - |
dc.date.issued | 2015-08 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/42650 | - |
dc.description.abstract | Purpose This 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 Methods Patients 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. Results Thirty-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 a parts per thousand yen3 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. Conclusion The 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. | - |
dc.publisher | SPRINGER | - |
dc.subject | SQUAMOUS-CELL CARCINOMA | - |
dc.subject | HTLV-1-INFECTED T-CELLS | - |
dc.subject | ADVANCED SOLID TUMORS | - |
dc.subject | MULTIPLE-MYELOMA | - |
dc.subject | SELECTIVE AURORA | - |
dc.subject | B ACTIVITY | - |
dc.subject | OVEREXPRESSION | - |
dc.subject | GROWTH | - |
dc.subject | COMBINATION | - |
dc.subject | SUPPRESSES | - |
dc.title | Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, WS[Kim, Won Seog] | - |
dc.identifier.doi | 10.1007/s10637-015-0258-y | - |
dc.identifier.scopusid | 2-s2.0-84944441520 | - |
dc.identifier.wosid | 000357462700017 | - |
dc.identifier.bibliographicCitation | INVESTIGATIONAL NEW DRUGS, v.33, no.4, pp.942 - 953 | - |
dc.relation.isPartOf | INVESTIGATIONAL NEW DRUGS | - |
dc.citation.title | INVESTIGATIONAL NEW DRUGS | - |
dc.citation.volume | 33 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 942 | - |
dc.citation.endPage | 953 | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | SQUAMOUS-CELL CARCINOMA | - |
dc.subject.keywordPlus | HTLV-1-INFECTED T-CELLS | - |
dc.subject.keywordPlus | ADVANCED SOLID TUMORS | - |
dc.subject.keywordPlus | MULTIPLE-MYELOMA | - |
dc.subject.keywordPlus | SELECTIVE AURORA | - |
dc.subject.keywordPlus | B ACTIVITY | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | COMBINATION | - |
dc.subject.keywordPlus | SUPPRESSES | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | Phase 1 clinical trial | - |
dc.subject.keywordAuthor | Alisertib | - |
dc.subject.keywordAuthor | Cancer | - |
dc.subject.keywordAuthor | Asian | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(03063) 25-2, SUNGKYUNKWAN-RO, JONGNO-GU, SEOUL, KOREAsamsunglib@skku.edu
COPYRIGHT © 2021 SUNGKYUNKWAN UNIVERSITY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.