{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:00:09Z","timestamp":1772571609910,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical Co., Ltd.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75\u00a0mg\/day, and the dose was increased daily to 7.5, 15 and 30\u00a0mg\/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500\u00a0ml, at which point the patient proceeded to the maintenance phase of 5\u20137\u00a0days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The mean change from baseline in body weight was maintained below 0\u00a0kg throughout the study. The mean change (\u00b1standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45\u00a0\u00b1\u00a0868.14\u00a0ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum: 1589.3\u00a0ml, minimum: 3.83\u00a0ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum: \u22122304.3\u00a0ml, minimum: \u221227.5\u00a0ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75\u201330\u00a0mg\/day.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyaa196","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T11:09:41Z","timestamp":1601636981000},"page":"354-362","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and safety of tolvaptan in patients with malignant ascites: a phase 2, multicenter, open-label, dose-escalation study"],"prefix":"10.1093","volume":"51","author":[{"given":"Toshihiro","family":"Kudo","sequence":"first","affiliation":[{"name":"Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan"},{"name":"Department of Medical Oncology, Osaka International Cancer Institute, Osaka Prefectural Hospital Organization, Osaka, 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