{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:44:48Z","timestamp":1790829888407,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011082","name":"School of Medicine, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Adavosertib (AZD1775) is an inhibitor of the Wee1 kinase. The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate\u2010risk\/high\u2010risk, locally advanced head and neck squamous cell carcinoma (HNSCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve patients with intermediate\u2010risk\/high\u2010risk HNSCC were enrolled, including those with p16\u2010negative tumors of the oropharynx, p16\u2010positive tumors of the oropharynx with\u00a0\u226510 tobacco pack\u2010years, and tumors of the larynx\/hypopharynx regardless of p16 status. All patients were treated with an 8\u2010week course of concurrent intensity\u2010modulated radiotherapy at 70 grays (Gy) (2 Gy daily in weeks 1\u20107), cisplatin 30 mg\/m<jats:sup>2<\/jats:sup> weekly (in weeks 1\u20107), and adavosertib (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8). The primary objective was to determine the maximum tolerated dose and the recommended phase 2 dose of adavosertib given concurrently with radiation and cisplatin. Secondary objectives were to determine the 12\u2010week objective response rate and progression\u2010free and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three patients (25%) experienced a dose\u2010limiting toxicity, including febrile neutropenia (n = 2) and grade 4 thromboembolism (n = 1). Two dose\u2010limiting toxicities occurred with adavosertib at 150 mg. The median follow\u2010up was 14.7 months. The 12\u2010week posttreatment objective response rate determined by positron emission tomography\/computed tomography was 100%. The 1\u2010year progression\u2010free and overall survival rates were both 90%. The maximum tolerated dose of adavosertib was 100 mg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Adavosertib 100 mg (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8), in combination with 70 Gy of intensity\u2010modulated radiotherapy and cisplatin 30 mg\/m<jats:sup>2<\/jats:sup>, is the recommended phase 2 dose for patients with HNSCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33789","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T12:22:41Z","timestamp":1628684561000},"page":"4447-4454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Phase 1 trial of adavosertib (AZD1775) in combination with concurrent radiation and cisplatin for intermediate\u2010risk and high\u2010risk head and neck squamous cell carcinoma"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-7986","authenticated-orcid":false,"given":"Bhishamjit S.","family":"Chera","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-2309","authenticated-orcid":false,"given":"Siddharth H.","family":"Sheth","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"},{"name":"Department of Medicine Division of Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shetal A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"},{"name":"Department of Medicine Division of Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Goldin","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0225-6064","authenticated-orcid":false,"given":"Kathe E.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette J.","family":"Shen","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"},{"name":"Department of Medicine Division of Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaorav P.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic T.","family":"Moore","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juneko E.","family":"Grilley Olson","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"},{"name":"Department of Medicine Division of Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-4447","authenticated-orcid":false,"given":"Jared M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center University of North Carolina Hospitals Chapel Hill North Carolina"},{"name":"Department of Medicine Division of Oncology University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 2","author":"National Comprehensive Cancer Network (NCCN)","year":"2014"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.62.2290"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0735-T"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0279"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0650"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-156"},{"key":"e_1_2_8_9_1","volume-title":"AZD1775 Investigator's Brochure","author":"AstraZeneca","year":"2015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073770"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00730"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3796"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.1025"},{"issue":"4","key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"S1168","DOI":"10.1016\/j.annonc.2020.08.2269","article-title":"LBA39 3\u2010years follow\u2010up of double\u2010blind randomized phase II comparing concurrent high\u2010dose cisplatin chemo\u2010radiation plus xevinapant or placebo in high\u2010risk patients with locally advanced squamous cell carcinoma of the head and neck [abstract]","volume":"31","author":"Bourhis J","year":"2020","journal-title":"Ann Oncol"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.9457"},{"key":"e_1_2_8_17_1","volume-title":"NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae): Head and Neck Cancers","author":"National Comprehensive Cancer Network (NCCN)","year":"2018"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25189"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2006.03.010"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq219"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21224"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33789","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33789","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:49:16Z","timestamp":1760269756000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":20,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/cncr.33789"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33789","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]},"assertion":[{"value":"2021-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}