A phase I clinical and pharmacokinetic study of brequinar sodium,DUP 785 (NSC 368390), using a weekly and a biweekly schedule |
| |
| Affiliation: | 1. Center of Clinical Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Hufelandstr. 55, 45147 Essen, Germany;2. Department of Epidemiology, Boston University School of Public Health, 715 Albany St, Boston, MA 02118, USA;3. Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partnerstandort Universitätsklinikum Essen, 45122 Essen, Germany;4. Center for Dermato-oncology, Department of Dermatology, University Hospital Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany;5. University of Strathclyde Institute of Global Public Health at iPRI International Prevention Research Institute, Espace Européen d’Ecully, Bâtiment G Allée Claude Debussy, 69130 Ecully ouest Lyon, France;6. Institute of Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Hufelandstr. 55, 45147 Essen, Germany;1. University Hospital of Pointe-à-Pitre, Neurology Department, Route de Chauvel, 97139 Abymes Guadeloupe, France;2. University Hospital of Bordeaux, Department of Medical Pharmacology, Pharmacovigilance, Center, INSERM U1219, F-33000, Bordeaux, France;3. Pathology Center, Cours Nolivos 97100 Basse-Terre, Guadeloupe, France;1. Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China;2. Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China |
| |
| Abstract: | ![]()
Brequinar, DUP 785, is a substituted 4-quinoline carboxylic acid derivative which in preclinical studies has shown broad antitumor activity. It is a novel antimetabolite blocking pyrimidine nucleotide synthesis. In a clinical phase I study, 83 patients were treated on a weekly schedule and 18 patients on a biweekly schedule. The drug was given intravenously as a short infusion. Three patients were entered on each dose level from a starting dose of 6 mg/m2 up to 2600 mg/m2 weekly. The dose ranges on a biweekly schedule were 500–850 mg/m2. There was no dose escalation in individual patients. Pharmacokinetic studies were performed in 19 patients on a weekly schedule and in two patients on a biweekly schedule. A biphasic decay in plasma was observed with a median half life of 10 h (5.1–23.4). The main dose-limiting toxicity was thrombocytopenia. Of non-hematologic side-effects, stomatitis/mucositis occurred frequently. Skin eruptions occurred rarely, but were a major problem when found. All side-effects were fully reversible; there were no signs of cumulative toxicity. Antitumor activity was observed in one patient with a lung metastasis from a bladder cancer and in a patient with an unknown primary tumor. The recommended doses for phase II trials with DUP 785 are: 1500–2000 mg/m2 on a weekly schedule and 500–750 mg/m2 on a biweekly schedule dependent on status before treatment. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
