{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T06:03:06Z","timestamp":1794204186502,"version":"4.8.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Treatment options are limited for recurrent\/metastatic adenoid cystic carcinoma of the head and neck (R\/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all\u2010trans retinoic acid (ATRA) combined with low\u2010dose apatinib in patients with R\/M ACCHN according to a secondary analysis of a phase II study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment\u2010related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25\u2009mg\/m<jats:sup>2<\/jats:sup>\/day) and apatinib (250\u2009mg\/day) between March 2019 and October 2021 until progression of disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 16 patients were included with nine (56.3%) males and aged 35\u201369\u2009years old. All recruited patients previously received anti\u2010angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow\u2010up of 23.9\u00a0months (range:17.8\u201331.7\u00a0months), 11 (68.8%) patients developed PD and one of them died in 20.9\u2009months. The median of progression\u2010free survival (PFS) was 16.3\u2009months (95% CI: 7.2\u201325.4\u2009months), and the 6\u2010month, 12\u2010month, and 24\u2010month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (<jats:italic>n<\/jats:italic>\u00a0=\u00a02, 12.5%) and hand\u2010foot syndrome (<jats:italic>n<\/jats:italic>\u00a0=\u00a01, 6.25%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>All\u2010trans retinoic acid combined with low\u2010dose apatinib might be a potential efficacy therapeutic option for patients with R\/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT 04433169).<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5653","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T10:42:04Z","timestamp":1675420924000},"page":"9144-9155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Combined all\u2010trans retinoic acid with low\u2010dose apatinib in treatment of recurrent\/metastatic head and neck adenoid cystic carcinoma: A single\u2010center, secondary analysis of a phase II study"],"prefix":"10.1002","volume":"12","author":[{"given":"Lulu","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjin","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wantao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4770-9458","authenticated-orcid":false,"given":"Guopei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"National Center for Stomatology  Shanghai China"},{"name":"National Clinical Research Center for Oral Diseases  Shanghai China"},{"name":"Shanghai Key Laboratory of Stomatology &amp; Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1054\/ijom.2003.0448"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e3181d26d45"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27408"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23925"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00020840-200404000-00013"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2007.12.057"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.01.001"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2021.188523"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.4248\/IJOS10005"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2011.01939.x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-529"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2015.51.4.2320599"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S97235"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359211013626"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130303"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18636-w"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2018.1509201"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0277-x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.01.039"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180939"},{"issue":"3","key":"e_1_2_12_22_1","first-page":"773","article-title":"Establishment of patient\u2010derived xenograft models of adenoid cystic carcinoma to assess pre\u2010clinical efficacy of combination therapy of a PI3K inhibitor and retinoic acid","volume":"11","author":"Sun B","year":"2021","journal-title":"Am J Cancer Res"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105366"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3758"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3415"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.9536"},{"key":"e_1_2_12_27_1","volume-title":"Head and Neck Cancers","author":"NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)","year":"2021"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.21674"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00584"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0407"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920927602"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01859"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32754"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23577"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-020-00925-2"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62961-5"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3145182"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12080707"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.167502"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.01.009"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201202014"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2010.07.003"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00541"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5653","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.5653","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5653","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:49:13Z","timestamp":1692582553000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.5653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/cam4.5653"],"URL":"https:\/\/doi.org\/10.1002\/cam4.5653","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]},"assertion":[{"value":"2022-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}