Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours
| Autor: | Dominique de Valeriola, E. Brendel, Martine Piccart, Thierry Gil, M Mano, C. G. Haase, Brian Schwartz, S. Bartholomeus, Dirk Strumberg, Ahmad Awada, Alain Hendlisz |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Pyridines efficacy Benzenesulfonates -- pharmacokinetics Pyridines -- pharmacokinetics Gastroenterology Benzenesulfonates -- administration & dosage Renal cell carcinoma Neoplasms Pyridines -- adverse effects Clinical Studies Pyridines -- administration & dosage solid tumours Benzenesulfonates Sorafenib Sciences bio-médicales et agricoles Middle Aged Kidney Neoplasms Oncology Female Safety Off Treatment pharmacokinetics medicine.drug Niacinamide safety Adult medicine.medical_specialty Benzenesulfonates -- adverse effects Maximum Tolerated Dose Efficacy Drug Administration Schedule Pharmacokinetics Refractory Kidney Neoplasms -- drug therapy Internal medicine Carcinoma medicine Humans Adverse effect Carcinoma Renal Cell Aged Solid tumours targeted agent business.industry Phenylurea Compounds medicine.disease Carcinoma Renal Cell -- drug therapy Surgery Neoplasms -- drug therapy business Bay BAY 43-9006 Targeted agent |
| Zdroj: | British Journal of Cancer, 92 (10 British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6602584 |
| Popis: | BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and tumour angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients with advanced, refractory solid tumours. BAY 43-9006 was administered daily for repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma were determined during the first treatment cycle. The most frequently reported adverse events over multiple cycles were gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400 mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state conditions were reached within 7 days. BAY 43-9006 exposure increased nonproportionally with increasing dose. In all, 32 patients were evaluated for tumour response: 15 patients showed tumour progression, 16 patients experienced stable disease (>6 months in eight patients), and one patient with renal cell carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days off treatment was safe, well tolerated, and showed antitumour activity. Clinical Trial Clinical Trial, Phase I Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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