{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:35:13Z","timestamp":1790638513717,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Multiple preclinical studies have shown cytotoxic synergy involving combinations of poly (ADP-ribose) polymerase (PARP) inhibitors and topoisomerase 1 (TOP1) inhibitors, but such combinations have proven too toxic in clinical trials. Liposomal irinotecan (nal-IRI) achieved similar intratumoral exposure with better antitumor activity than the conventional TOP1 inhibitor irinotecan in preclinical models. Tumor targeted delivery of TOP1 inhibitor using nal-IRI and an intermittent schedule of administration of PARP inhibitor may provide a tolerable combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A phase I study was performed to evaluate the safety and tolerability of escalating doses of nal-IRI and the PARP inhibitor veliparib in patients with solid tumors resistant to standard treatments. Nal-IRI was administered on days 1 and 15 and veliparib on days 5-12 and 19-25 in 28-day cycles.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eighteen patients were enrolled across 3 dose levels. Five patients encountered dose\u2013limiting toxicities, including grade 3 diarrhea lasting more than 72 h in 3 patients and 1 patient each with grade 4 diarrhea and grade 3 hyponatremia. The most common grade 3 or 4 toxicities included diarrhea (50% of patients), nausea (16.6%), anorexia, and vomiting (11.1% each) (Table 1). There was no difference in frequencies of adverse events based on UGT1A1*28 status or prior opioid use (Table 1).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The clinical trial was terminated due to high frequency of unacceptable gastrointestinal toxicities, which precluded dose escalation of veliparib in combination with nal-IRI (ClinicalTrials.gov Identifier: NCT02631733).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyad023","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T17:12:44Z","timestamp":1680541964000},"page":"460-e298","source":"Crossref","is-referenced-by-count":9,"title":["A Phase I Study of a Combination of Liposomal Irinotecan and Veliparib in Solid Tumors"],"prefix":"10.1093","volume":"28","author":[{"given":"Meredith","family":"LaRose","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Columbia University Herbert Irving Comprehensive Cancer Center , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roisin M","family":"Connolly","sequence":"additional","affiliation":[{"name":"Cancer Research @UCC, College of Medicine and Health, University College Cork , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara C","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic , Rochester, MN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsidhar","family":"Velcheti","sequence":"additional","affiliation":[{"name":"Thoracic Medical Oncology, Perlmutter Cancer Center, NYU Langone , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasa","family":"Vilimas","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Branch, Center for Cancer Research, NCI , Bethesda, MD 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