{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T06:27:47Z","timestamp":1766557667940},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:p> PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. <\/jats:p><jats:p> PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg\/m<jats:sup>2<\/jats:sup>. All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. <\/jats:p><jats:p> RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L\/h\u00b7m<jats:sup>2<\/jats:sup>. The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg\/m<jats:sup>2<\/jats:sup>. <\/jats:p><jats:p> CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg\/m<jats:sup>2<\/jats:sup> every 3 weeks in patients previously treated with chemotherapy. <\/jats:p>","DOI":"10.1200\/jco.2000.18.23.3986","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:57:30Z","timestamp":1487919450000},"page":"3986-3992","source":"Crossref","is-referenced-by-count":17,"title":["Phase I and Pharmacokinetic Study of the Camptothecin Analog DX-8951f Administered as a 30-Minute Infusion Every 3 Weeks in Patients With Advanced Cancer"],"prefix":"10.1200","volume":"18","author":[{"given":"Val\u00e9rie","family":"Boige","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Raymond","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Faivre","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Gatineau","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Meely","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Mekhaldi","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Pautier","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Ducreux","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Rixe","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"Armand","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Gustave Roussy Institute, Villejuif, France, and Clinical Research Department, Daiichi Pharmaceuticals UK Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1-0539","doi-asserted-by":"publisher","DOI":"10.1021\/ja00968a057"},{"key":"R2-0539","doi-asserted-by":"crossref","unstructured":"Hsiang  YH,   Hertzberg  R,   Hecht  S,  et al:  Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.   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