A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours
| Autor: | Marvin B. Cohen, A. du Bois, T Schaller-Kranz, B Jung, N. Frickhofen, A Loehr |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Maximum Tolerated Dose Nausea cisplatin Neutropenia Gastroenterology taxane chemistry.chemical_compound Pharmacokinetics BMS-188797 Internal medicine Neoplasms Clinical Studies Antineoplastic Combined Chemotherapy Protocols medicine Humans Infusions Intravenous Aged Cervical cancer Cisplatin Taxane business.industry Middle Aged medicine.disease Oncology Paclitaxel chemistry Anesthesia Female Taxoids medicine.symptom business Febrile neutropenia medicine.drug Half-Life |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2). |
| Databáze: | OpenAIRE |
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