A Phase I Study to Characterize the Safety, Tolerability, and Pharmacokinetics of Topotecan at 4 mg/m2Administered Weekly as a 30-Minute Intravenous Infusion in Patients With Cancer
| Autor: | Jean T. Hartney, Donald W. Northfelt, Mitesh J. Borad, Kelly K. Curtis, P. P. Griffin, Tom R. Fitch, Peter F. Lebowitz, Roxanne C. Jewell, Jung W. Park |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male endocrine system diseases Metabolic Clearance Rate Anemia Biological Availability Antineoplastic Agents Pharmacology Drug Administration Schedule Pharmacokinetics Neoplasms Humans Medicine Pharmacology (medical) In patient Infusions Intravenous Adverse effect Chromatography High Pressure Liquid Fatigue Aged Aged 80 and over Leukopenia Dose-Response Relationship Drug business.industry Cancer Drug Tolerance Middle Aged medicine.disease Thrombocytopenia Phase i study Female Topotecan medicine.symptom business medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 50:268-275 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270009343699 |
| Popis: | Topotecan pharmacokinetics at higher infusion rates (4 mg/m2 over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4-mg/m2 topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, V(ss), C(max), t(max), t(1/2), AUC(0-t), and AUC(0-infinity). Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, V(ss) value of 101 L, and t(1/2) value of 5.0 h. Nine significant adverse events (all hematologic) were topotecan related. Grade 3 or less adverse events included anemia, thrombocytopenia, leukopenia, and fatigue. Pharmacokinetics of the 4-mg/m2 infusion of topotecan over 30 minutes are comparable to findings from studies of lower and higher doses. Toxicities are similar to previous reports. |
| Databáze: | OpenAIRE |
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