{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:32:20Z","timestamp":1777566740879,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,4,30]],"date-time":"2012-04-30T00:00:00Z","timestamp":1335744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">BCX<\/jats:styled-content>1777 (forodesine), a novel purine nucleoside phosphorylase inhibitor, induces apoptosis, mainly in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells. To evaluate the safety, tolerability, and pharmacokinetics of <jats:styled-content style=\"fixed-case\">BCX<\/jats:styled-content>1777, we conducted a phase I study in patients with relapsed or refractory peripheral <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\/natural killer\u2010cell malignancies. Eligible patients had relapsed or refractory peripheral <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\/natural killer\u2010cell malignancies without any major organ dysfunction. <jats:styled-content style=\"fixed-case\">BCX<\/jats:styled-content>1777 was administered orally once daily (dose escalation: 100, 200, and 300\u00a0mg) until disease progression requiring new therapy or unacceptable adverse events occurred. A total of 13 patients were enrolled and treated in three dose cohorts (100\u00a0mg\/day, five patients; 200\u00a0mg\/day, three patients; 300\u00a0mg\/day, five patients). Although none of the patients developed dose\u2010limiting toxicities, further dose escalation was not performed based on data from overseas. Therefore, the maximum tolerated dose was not determined. Adverse events of grade 3 or greater (\u22652 patients) included lymphopenia (62%), anemia (15%), leukopenia (8%), and pyrexia (8%). Plasma pharmacokinetics parameter of <jats:styled-content style=\"fixed-case\">BCX<\/jats:styled-content>1777 (area under the plasma concentration\u2010time curve) at day 1 in each cohort was 1948\u00a0\u00b1\u00a0884, 4608\u00a0\u00b1\u00a01030, and 4596\u00a0\u00b1\u00a0939\u00a0ng\u2022h\/mL, respectively. Disease control was achieved in approximately half of patients. One patient with anaplastic large cell lymphoma, which was negative for anaplastic lymphoma kinase, achieved a complete response, and two patients with cutaneous <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell lymphoma achieved partial responses. <jats:styled-content style=\"fixed-case\">BCX<\/jats:styled-content>1777 was well tolerated at doses up to 300\u00a0mg once daily and showed preliminary evidence of activity in relapsed or refractory peripheral <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\/natural killer\u2010cell malignancies, warranting further investigation. (<jats:italic>Cancer Sci<\/jats:italic> 2012; 103: 1290\u20131295)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2012.02287.x","type":"journal-article","created":{"date-parts":[[2012,3,26]],"date-time":"2012-03-26T23:01:44Z","timestamp":1332802904000},"page":"1290-1295","source":"Crossref","is-referenced-by-count":18,"title":["Phase <scp>I<\/scp> study of <scp>BCX<\/scp>1777 (forodesine) in patients with relapsed or refractory peripheral <scp>T<\/scp>\/natural killer\u2010cell malignancies"],"prefix":"10.1111","volume":"103","author":[{"given":"Michinori","family":"Ogura","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Tsukasaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Science Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Nagai","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya Daini Red Cross Hospital Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Science Nagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Stem Cell Transplantation National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomitsu","family":"Hotta","sequence":"additional","affiliation":[{"name":"National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensei","family":"Tobinai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Stem Cell Transplantation National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"45","article-title":"Purine nucleoside phosphorylase deficiency","volume":"3","author":"Markert ML","year":"1991","journal-title":"Immunodefic Rev"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.10.83"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V110.11.122.122","article-title":"Response to oral forodesine in refractory cutaneous T\u2010cell lymphoma: interim results of a phase I\/II study (Abstract)","volume":"110","author":"Duvic 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