{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T01:32:46Z","timestamp":1778808766254,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent\/refractory lymphoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The authors escalated the dose of CXD101 from 1 mg twice daily orally for 5 days in a 21\u2010day cycle (3+3 design).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 39 patients were enrolled, 36 of whom received CXD101. Of the 30 patients in the escalation cohort, 29 were evaluable for determination of the dose\u2010limiting toxicity (DLT). DLTs were noted at doses of 16 mg twice daily (1 of 6 patients), 20 mg twice daily (1 of 6 patients), and 24\/25 mg twice daily (2 of 5 patients, both of whom developed neutropenic fever). The MTD was 20 mg twice daily, which achieved maximal plasma concentrations (\u00b1standard deviation) of 231\u00b176 nM to 342\u00b1126 nM, which was within the biologically active range. Six patients received 20 mg twice daily in an expansion cohort. The most frequent adverse events were fatigue, nausea, and reversible cytopenia. Key grade 3 to 4 adverse events (according to Common Terminology Criteria for Adverse Events criteria [version 4.03]) included thrombocytopenia (11%), neutropenia (17%), and neutropenic fever (2%) across the 133 CXD101 cycles given. The toxicity profile was similar to that of licensing studies with other histone deacetylase inhibitors. In 22 evaluable patients receiving a dose of \u226516 mg twice daily (17 of whom had lymphoma and 5 of whom had solid tumors), 3 partial responses (2 in patients with classic Hodgkin lymphoma after allogenic stem cell transplantation and 1 in a patient with angioimmunoblastic T\u2010cell lymphoma) and 1 complete response (in a patient with follicular lymphoma) were noted (overall response rate of 18%) in addition to 9 patients who achieved durable stable disease. Responses were noted predominantly among patients with lymphoma (tumor reduction noted in 63% of patients on standard computed tomography).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The MTD in the current study was found to be 20 mg twice daily. Encouraging and durable activity was observed in patients with Hodgkin lymphoma, T\u2010cell lymphoma, and follicular lymphoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31791","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T15:36:51Z","timestamp":1539790611000},"page":"99-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A phase 1 study to assess the safety, tolerability, and pharmacokinetics of CXD101 in patients with advanced cancer"],"prefix":"10.1002","volume":"125","author":[{"given":"Toby A.","family":"Eyre","sequence":"first","affiliation":[{"name":"Early Phase Trials Unit, Churchill Hospital University of Oxford  Oxford United Kingdom"},{"name":"Department of Clinical Haematology, Oxford Cancer Centre Churchill Hospital  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham P.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oxford Cancer Centre Churchill Hospital  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avinash","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Christie NHS Hospital Trust  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Coupe","sequence":"additional","affiliation":[{"name":"Early Phase Trials Unit, Churchill Hospital University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semira","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology, Oxford Cancer Centre Churchill Hospital  Oxford United Kingdom"},{"name":"Laboratory of Cancer Biology University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Whittaker","sequence":"additional","affiliation":[{"name":"Celleron Therapeutics Ltd  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai Mun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology Oxford University Hospitals NHS Trust  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia","family":"Campo","sequence":"additional","affiliation":[{"name":"GCP Laboratory, Department of Oncology University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Soilleux","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology Oxford University Hospitals NHS Trust  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn","family":"Tysoe","sequence":"additional","affiliation":[{"name":"Early Phase Trials Unit, Churchill Hospital University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Cousins","sequence":"additional","affiliation":[{"name":"Early Phase Trials Unit, Churchill Hospital University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"La Thangue","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology University of Oxford  Oxford United Kingdom"},{"name":"Celleron Therapeutics Ltd  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa K.","family":"Folkes","sequence":"additional","affiliation":[{"name":"CRUK\/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Department of Oncology University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R. L.","family":"Stratford","sequence":"additional","affiliation":[{"name":"CRUK\/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, Department of Oncology University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Kerr","sequence":"additional","affiliation":[{"name":"Celleron Therapeutics Ltd  Oxford United Kingdom"},{"name":"Nuffield Division of Clinical Laboratory Sciences, Academic Block University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Middleton","sequence":"additional","affiliation":[{"name":"Early Phase Trials Unit, Churchill Hospital University of Oxford  Oxford United Kingdom"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/15592294.2014.983367"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2007.01.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.545"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00092"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.4223"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.6150"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.2782"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-025999"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.10.2434"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.154377"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-008-9131-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14611"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.05.008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.313"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0709"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-4868-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2133"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.12.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913912107"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.2395"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2403"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.1350"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0122"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.08.001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp200329f"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv237"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.31791","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.31791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T04:26:20Z","timestamp":1761884780000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.31791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,17]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/cncr.31791"],"URL":"https:\/\/doi.org\/10.1002\/cncr.31791","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,17]]},"assertion":[{"value":"2018-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}