{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:09:49Z","timestamp":1790359789037,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T00:00:00Z","timestamp":1432512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>\n                    We carried out a multicenter dose\u2010escalation phase I study of oral\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose (\n                    <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>\n                    ), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 at doses of 1, 2, 3, 4, and 6\u00a0mg in the \u201c3\u00a0+\u00a03\u201d dose escalation design. The most common treatment\u2010related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug\u2010related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The\n                    <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>\n                    was 6\u00a0mg, with dose\u2010limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1\u20132 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4\u00a0mg.\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 was rapidly absorbed, and exposure tended to increase in a dose\u2010dependent manner. Accumulation of\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 was seen with 4\u00a0weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the\n                    <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>\n                    of\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 was 6\u00a0mg.\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 was safe and well tolerated in a dose range of 1\u20134\u00a0mg. However, long\u2010term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of\n                    <jats:styled-content style=\"fixed-case\">OPB<\/jats:styled-content>\n                    \u201051602 for hematological malignancies with a daily dosing schedule was terminated.\n                  <\/jats:p>","DOI":"10.1111\/cas.12683","type":"journal-article","created":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T15:14:17Z","timestamp":1429802057000},"page":"896-901","source":"Crossref","is-referenced-by-count":100,"title":["Phase I study of\n                    <scp>OPB<\/scp>\n                    \u201051602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed\/refractory hematological malignancies"],"prefix":"10.1111","volume":"106","author":[{"given":"Michinori","family":"Ogura","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Terui","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Cancer Institute Hospital Japanese Foundation For Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Nagoya University Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Hematology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology University Hospital Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Takamatsu","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Hematology and Infectious Disease Fukuoka University Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Naoe","sequence":"additional","affiliation":[{"name":"Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensei","family":"Tobinai","sequence":"additional","affiliation":[{"name":"Hematology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Munakata","sequence":"additional","affiliation":[{"name":"Hematology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Fujii Memorial Research Institute Otsuka Pharmaceutical Co., Ltd. Otsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Yuasa","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohiko","family":"Hatake","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Cancer Institute Hospital Japanese Foundation For Cancer Research Tokyo 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