{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:11:31Z","timestamp":1772748691455,"version":"3.50.1"},"reference-count":11,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,5,15]]},"abstract":"<jats:p> PURPOSE: Troxacitabine (Troxatyl, BCH-4556; BioChem Pharma Inc, Basingstoke, United Kingdom) is a novel synthetic l-nucleoside analog with activity against a broad range of human tumors in preclinical models. Preclinical toxicity suggested a predictable toxicity profile consistent with an agent of this class, with evidence of interspecies differences. We conducted a phase I study of troxacitabine given as a 30-minute infusion once every 21 days. <\/jats:p><jats:p> PATIENTS AND METHODS: The starting dose of troxacitabine was 0.025 mg\/m<jats:sup>2<\/jats:sup>, based on toxicology data from the most sensitive species studied (cynomolgus monkey). Doses were doubled until grade 1 skin or mucosal or grade 2 other toxicity was encountered. A modified Fibonacci scale was used. <\/jats:p><jats:p> RESULTS: A total of 45 patients were enrolled at 13 dose levels. Most common nonhematologic side effects were skin rash (44%), lethargy (29%), nausea (24%), alopecia, dry skin (18%), anorexia (13%), neurosensory symptoms (13%), and hand-foot syndrome (13%). In patients treated with prednisone 25 mg\/d orally for 5 days, starting on day 1, skin rash was less problematic. Two patients at 12.5 mg\/m<jats:sup>2<\/jats:sup> experienced dose-limiting (grade 4) granulocytopenia. Confirmed partial responses were documented in one patient with previously untreated renal cell carcinoma with metastatic lung and bone lesions and in one patient with an unknown primary tumor. Eighteen patients had a best response of stable disease with a median duration of 5.1 months (range, 2.1 to 18.7 months). <\/jats:p><jats:p> CONCLUSION: When given in this schedule, the maximum-tolerated dose of troxacitabine is 12.5 mg\/m<jats:sup>2<\/jats:sup>, and the recommended dose for additional phase II studies is 10 mg\/m<jats:sup>2<\/jats:sup> once every 21 days with steroid premedication. <\/jats:p>","DOI":"10.1200\/jco.2002.12.047","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T13:13:48Z","timestamp":1027775628000},"page":"2567-2574","source":"Crossref","is-referenced-by-count":19,"title":["Phase I and Pharmacokinetic Study of Novel <scp>l<\/scp>-Nucleoside Analog Troxacitabine Given as a 30-Minute Infusion Every 21 Days"],"prefix":"10.1200","volume":"20","author":[{"given":"Karl","family":"Belanger","sequence":"first","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Moore","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharyn D.","family":"Baker","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne","family":"Dionne","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Maclean","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Jolivet","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lillian","family":"Siu","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Souli\u00e8res","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Wainman","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"Seymour","sequence":"additional","affiliation":[{"name":"From the Centre Hospitalier de l\u2019Universite de Montreal, Montreal; Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Clinical Trials Group, Queen\u2019s University, Kingston; and BioChem Pharma Inc, Laval, Canada; and Cancer Therapy and Research Center, San Antonio, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1-108231","unstructured":"Grove  KL,   Liu  S-H,   Gao  Z,  et al:  Anticancer activity of \u03b2-Dioxolane-cytidine, a novel nucleoside analog with the unnatural L configuration.  Cancer Res 55:  3008,1995-3011,   l"},{"key":"R2-108231","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008387019062"},{"key":"R3-108231","unstructured":"Rabbani  SA,   Harakidas  P,   Bowlin  T,  et al:  Effect of nucleoside analog BCH-4556 on prostate cancer growth and metastases in vitro and in vivo.  Cancer Res 58:  3461,1998-3465,"},{"key":"R4-108231","unstructured":"Kadhim  SA,   Bowlin  TL,   Waud  WR,  et al:  Potent antitumour activity of a novel nucleoside analog, BCH-4556, in human renal cell carcinoma xenograft tumor models.  Cancer Res 57:  4803,1997-4810,"},{"key":"R5-108231","unstructured":"Bowlin  T,   Genne  P,   Kadhim  S,  et al:  A novel cytidine nucleoside analog, BCH-4556, with potent activity against human anthracycline-resistant leukemia.  Proc Annu Meet Am Assoc Cancer Res 38:  100,1997  (abstr 668)"},{"key":"R6-108231","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.23055"},{"key":"R7-108231","unstructured":"Gourdeau  H,   Clarke  ML,   Ouellet  F,  et al:  Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analog, in human leukemic and solid tumor cell lines.  Cancer Res 61:  7217,2001-7214,"},{"key":"R8-108231","unstructured":"Grove  KL,   Cheng  YC:   Uptake and metabolism of the new anticancer compound \u03b2-dioxolane-cytidine in human prostate carcinoma DU-145 cells.  Cancer Res 56:  4187,1996-91,   l"},{"key":"R11-108231","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"R12-108231","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.96"},{"key":"R13-108231","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.3.762"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2002.12.047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T20:37:31Z","timestamp":1653511051000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2002.12.047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,15]]},"references-count":11,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2002,5,15]]}},"alternative-id":["10.1200\/JCO.2002.12.047"],"URL":"https:\/\/doi.org\/10.1200\/jco.2002.12.047","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,15]]}}}