{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:04:32Z","timestamp":1785179072555,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"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":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      This phase 1 study aimed to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary efficacy of rucaparib (RUB), a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, combined with liposomal irinotecan (nal\u2010IRI) and 5\u2010fluorouracil (5\u2010FU) in metastatic gastrointestinal (GI) cancers. RUB targets DNA repair pathways, showing efficacy in tumors with homologous recombination deficiency, such as\n                      <jats:italic>BRCA<\/jats:italic>\n                      mutations. Preclinical data suggest synergy with irinotecan, but overlapping toxicities pose challenges.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighteen patients with metastatic GI cancers, who previously progressed on at least one systemic therapy, were enrolled. A novel sequential dosing regimen, informed by nal\u2010IRI pharmacokinetic analysis, was used. Twelve patients were evaluable for dose\u2010limiting toxicity (DLT) and 12 for response per Response Evaluation Criteria in Solid Tumors v1.1 criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The MTD was established as RUB 600 mg twice daily, nal\u2010IRI 50 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , and 5\u2010FU 2400 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 46 hours. The objective response rate (ORR) was 33% (4 of 12), and the disease control rate (DCR) was 75% (9 of 12). Common grade 3 adverse events included diarrhea (33%) and neutropenia (25%), with no grade 4\/5 events. Responses were notable in patients with somatic\n                      <jats:italic>ATM<\/jats:italic>\n                      and\n                      <jats:italic>BRCA<\/jats:italic>\n                      mutations, especially those with prior platinum exposure. No DLTs occurred at the recommended phase 2 dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This optimized dosing schedule successfully established the MTD for RUB with nal\u2010IRI and 5\u2010FU, overcoming prior challenges with PARP inhibitor and irinotecan combinations. The promising ORR and DCR support further evaluation of this regimen in advanced GI malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70184","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T13:04:16Z","timestamp":1763816656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimized dose schedule of rucaparib and liposomal irinotecan\/5\u2010fluorouracil in metastatic gastrointestinal cancers: A phase 1 study"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-0841","authenticated-orcid":false,"given":"Cody","family":"Eslinger","sequence":"first","affiliation":[{"name":"Department of Hematology\u2010Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Walden","sequence":"additional","affiliation":[{"name":"Department of 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