{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T23:57:06Z","timestamp":1766102226330},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T00:00:00Z","timestamp":1359417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that \u22652\u00b75\u00a0\u03bcmol\/l concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high\u2010dose vorinostat could safely augment the anti\u2010tumour activity of (R)<jats:styled-content style=\"fixed-case\">ICE<\/jats:styled-content> [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400\u00a0mg\/d to 700\u00a0mg bid for 5\u00a0d in combination with the standard (R)<jats:styled-content style=\"fixed-case\">ICE<\/jats:styled-content> regimen (days 3, 4 and 5). Twenty\u2010nine patients [median age 56\u00a0years, median 2 prior therapies, 14 chemoresistant (of 27 evaluable), 2 prior transplants] were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500\u00a0mg twice daily\u00a0\u00d7\u00a05\u00a0d. Common dose limiting toxicities included infection (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), hypokalaemia (<jats:italic>n<\/jats:italic>\u00a0=\u00a02), and transaminitis (<jats:italic>n<\/jats:italic>\u00a0=\u00a02). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4\u00b75\u00a0\u03bcmol\/l (range 4\u00b72\u20136\u00b70\u00a0\u03bcmol\/l) and <jats:italic>in vitro<\/jats:italic> data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response\/unconfirmed complete response. High\u2010dose vorinostat can be delivered safely with (R)<jats:styled-content style=\"fixed-case\">ICE<\/jats:styled-content>, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted.<\/jats:p>","DOI":"10.1111\/bjh.12230","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T12:17:43Z","timestamp":1359461863000},"page":"183-191","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A phase I study of pulse high\u2010dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (<scp>ICE<\/scp>) in patients with relapsed lymphoma"],"prefix":"10.1111","volume":"161","author":[{"given":"Lihua E.","family":"Budde","sequence":"first","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"},{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle M.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Valley Medical Center Renton WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei R.","family":"Shustov","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"},{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Pagel","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"},{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted A.","family":"Gooley","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"},{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Radiology Massachusetts General Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara L.","family":"Chen","sequence":"additional","affiliation":[{"name":"Pharmacy Services University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy L.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer E.","family":"Roden","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britt E.","family":"Kammerer","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shani L.","family":"Frayo","sequence":"additional","affiliation":[{"name":"Clinical Research Dvision Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Warr","sequence":"additional","affiliation":[{"name":"Great Falls Clinic Great Falls MT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Yakima Regional Medical &amp; 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