{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:36:09Z","timestamp":1790418969917,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U54CA168512"],"award-info":[{"award-number":["U54CA168512"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,4,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1\/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2\u20106 [D2\u20106]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re\u2010escalation in cohort C. In arm 2, patients were assigned to NIR (days 1\u20107 [D1\u20107]) and escalating doses of IRN (D2\u20106).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose\u2010limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for &gt;7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1\u20107 plus TMZ at 30 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      every day on D2\u20106 (arm 1) or NIR at 100 mg every day on D1\u20107 plus IRN at 20 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      every day on D2\u20106 (arm 2). One confirmed partial response was observed in arm 2; the median progression\u2010free survival was 9.0 weeks (95% CI, 7.0\u201010.1 weeks) and 16.3 weeks (95% CI, 5.1\u201069.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP\u2010ribose) activity was 89% (range, 83%\u201098%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple\u2010combination study of NIR, IRN, and TMZ has commenced.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.33349","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T22:33:46Z","timestamp":1607466826000},"page":"1301-1310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["SARC025 arms 1 and 2: A phase 1 study of the poly(ADP\u2010ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma"],"prefix":"10.1002","volume":"127","author":[{"given":"Rashmi","family":"Chugh","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla V.","family":"Ballman","sequence":"additional","affiliation":[{"name":"Population Health Sciences Weill Cornell Medicine New York New 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