Phase I and Pharmacokinetic Study of Paclitaxel by 24-Hour Intravenous Infusion
| Autor: | Atsuya Karato, Hitoshi Arioka, Hajime Nakashima, Hiroshi Kunikane, Kenji Eguchi, Tomohide Tamura, Nagahiro Saijo, Yuichiro Ohe, Makoto Nishio, Yasutsuna Sasaki, Tetsu Shinkai, Hironobu Omatsu |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Cancer Research Time Factors Paclitaxel Adolescent medicine.medical_treatment Pharmacology Article Ranitidine chemistry.chemical_compound Pharmacokinetics medicine Humans Infusions Intravenous Dexamethasone Aged Chemotherapy business.industry Diphenhydramine Half-life Middle Aged Oncology chemistry Phase I study Female Premedication business Agranulocytosis medicine.drug |
| Zdroj: | Japanese Journal of Cancer Research : Gann |
| ISSN: | 0910-5050 |
| Popis: | Paclitaxel, a new antitubular agent, appears to be one of the most promising single agents for the chemotherapy of various solid tumors. The primary objectives of this phase I study of paclitaxel using 24‐h continuous intravenous infusions were to determine the maximum tolerated dose of paclitaxel administered by this schedule to Japanese patients with solid tumors and to evaluate the pharmaco‐kiiietics of paclitaxel. Eighteen patients received one of five doses of paclitaxel, 49.5, 75, 105, 135 or 180 mg/m2. Prcmedication with diphenhydramine, dexamethasone, and ranitidine was used to prevent acute hypersensitivity reactions. Pharmacokinetic data were obtained from all 18 patients. Dose‐limiting toxicities observed at 180 mg/m2 consisted of grade 4 granulocytopenia associated with grade 3 infection. No severe HSRs or cardiac toxicity were detected. Reversible toxicities observed included liver dysfunction, alopecia, peripheral neuropathy and myalgias. Pharmacokinetic studies performed using high‐performance liquid chromatography demonstrated that plasma concentrations of paclitaxel increased during the 24‐h infusion and declined immediately upon cessation of the infusion with a half life of 13.1‐24.6 h (75‐180 mg/m2). Less than 10% of paclitaxel was excreted in the urine within 72 h. The peak plasma concentrations and the areas under the concentration‐versus‐time curves increased linearly with the dose administered. Antitumor activity was observed in one patient with pulmonary metastasis from pharyngeal cancer. Based on these studies a phase II trial dose of 135 mg/m2 administered over 24 h was chosen. |
| Databáze: | OpenAIRE |
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