{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T20:10:15Z","timestamp":1768594215278,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Clovis Oncology, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The poly(ADP-ribose) polymerase inhibitor rucaparib is approved for the treatment of patients with recurrent ovarian and metastatic castration-resistant prostate cancer; however, limited data are available on its use in patients with hepatic dysfunction. This study investigated whether hepatic impairment affects the pharmacokinetics, safety, and tolerability of rucaparib in patients with advanced solid tumors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients with normal hepatic function or moderate hepatic impairment according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria were enrolled and received a single oral dose of rucaparib 600\u00a0mg. Concentrations of rucaparib and its metabolite M324 in plasma and urine were measured. Pharmacokinetic parameters were compared between hepatic function groups, and safety and tolerability were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Sixteen patients were enrolled (<jats:italic>n<\/jats:italic>\u2009=\u20098 per group). Rucaparib maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) was similar, while the area under the concentration\u2013time curve from time 0 to infinity (AUC<jats:sub>0\u2013inf<\/jats:sub>) was mildly higher in the moderate hepatic impairment group than in the normal control group (geometric mean ratio, 1.446 [90% CI 0.668\u20133.131]); similar trends were observed for M324. Eight (50%) patients experienced \u2265\u20091 treatment-emergent adverse event (TEAE); 2 had normal hepatic function and 6 had moderate hepatic impairment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Patients with moderate hepatic impairment showed mildly increased AUC<jats:sub>0\u2013inf<\/jats:sub> for rucaparib compared to patients with normal hepatic function. Although more patients with moderate hepatic impairment experienced TEAEs, only 2 TEAEs were considered treatment related. These results suggest no starting dose adjustment is necessary for patients with moderate hepatic impairment; however, close safety monitoring is warranted.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-021-04278-2","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T09:03:39Z","timestamp":1619600619000},"page":"259-270","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacokinetics and safety of rucaparib in patients with advanced solid tumors and hepatic impairment"],"prefix":"10.1007","volume":"88","author":[{"given":"Nikolay","family":"Grechko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viera","family":"Skarbova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-9998","authenticated-orcid":false,"given":"Monika","family":"Tomaszewska-Kiecana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3199-2298","authenticated-orcid":false,"given":"Rodryg","family":"Ramlau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Centkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-9224","authenticated-orcid":false,"given":"Yvette","family":"Drew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-9843","authenticated-orcid":false,"given":"Rafal","family":"Dziadziuszko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-1035","authenticated-orcid":false,"given":"Milada","family":"Zemanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeri","family":"Beltman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Nash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenn","family":"Habeck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-1419","authenticated-orcid":false,"given":"Mingxiang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-2012","authenticated-orcid":false,"given":"Jim","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"issue":"13 suppl","key":"4278_CR1","doi-asserted-by":"publisher","first-page":"Abstract 2475","DOI":"10.1158\/1538-7445.AM2017-2475","volume":"77","author":"L Robillard","year":"2017","unstructured":"Robillard L, Nguyen M, Harding T, Simmons A (2017) In vitro and in vivo assessment of the mechanism of action of the PARP inhibitor rucaparib. 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Grechko, J. Beltman, E. Nash, J. Habeck, M. Liao, and J.J. Xiao are employees of Clovis Oncology and may own stock or have stock options in that company. Y. Drew is an employee of Newcastle University and has received royalty payments from Newcastle for her involvement in the development of rucaparib; she has served as an advisory board member and received research funding from Clovis Oncology. R. Dziadziuszko has received renumeration from AstraZeneca, Foundation Medicine, MSD, Novartis, Pfizer, Roche, Seattle Genetics, and Takeda. The other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Independent Ethics Committees (IEC).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study before participation.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}