{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:22:03Z","timestamp":1789611723477,"version":"build-2803163510"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src\/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR\u226560 ml\/min per 1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    , and total kidney volume \u2265750 ml were randomized 1:1:1 to bosutinib 200 mg\/d, bosutinib 400 mg\/d, or placebo for \u226424 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for \u22652 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg\/d were later reduced to 200 mg\/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg\/d versus placebo (1.63% versus 4.74%, respectively;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    =0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg\/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified. (ClinicalTrials.gov: NCT01233869).\n                  <\/jats:p>","DOI":"10.1681\/asn.2016111232","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T20:20:18Z","timestamp":1503606018000},"page":"3404-3413","source":"Crossref","is-referenced-by-count":71,"title":["Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"28","author":[{"given":"Vladimir","family":"Tesar","sequence":"first","affiliation":[{"name":"Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimierz","family":"Ciechanowski","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Pomeranian Medical University, Szczecin, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"York","family":"Pei","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Health Network, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Barash","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Shannon","sequence":"additional","affiliation":[{"name":"Worldwide Research and Development, Pfizer Inc, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Li","sequence":"additional","affiliation":[{"name":"Early Oncology Development and Clinical Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason H.","family":"Williams","sequence":"additional","affiliation":[{"name":"Worldwide Research and Development, Pfizer Inc, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Levisetti","sequence":"additional","affiliation":[{"name":"Worldwide Research and Development, Pfizer Inc, San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Arkin","sequence":"additional","affiliation":[{"name":"Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts; 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