Phase I trial of bortezomib in combination with docetaxel in patients with advanced solid tumors
| Autor: | Kimberly Dinh, John J. Wright, Deborah K. Armstrong, Michael A. Carducci, Lance K. Lassiter, Ross C. Donehower, Rana Sullivan, Wells A. Messersmith, Virna Almuete, Sharyn D. Baker |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Proteasome Endopeptidase Complex Cancer Research medicine.medical_specialty Metabolic Clearance Rate CYP3A Urology Docetaxel Pharmacology Bortezomib Cytochrome P-450 Enzyme System Pharmacokinetics Refractory Neoplasms hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols medicine Cytochrome P-450 CYP3A Humans neoplasms Fatigue Aged Dose-Response Relationship Drug business.industry Anemia Middle Aged medicine.disease Boronic Acids Treatment Outcome Oncology Area Under Curve Pyrazines Toxicity Proteasome inhibitor Female Taxoids business Proteasome Inhibitors Febrile neutropenia medicine.drug |
| Zdroj: | Clinical Cancer Research. 12:1270-1275 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-05-1942 |
| Popis: | PURPOSE: Bortezomib (PS-341), a first-in-class proteasome inhibitor, is metabolized by deboronation involving cytochrome P4503A (CYP3A), which also metabolizes docetaxel. Preclinical studies have shown synergy between bortezomib and taxanes. We conducted a phase I study combining bortezomib and docetaxel in refractory solid tumor patients. EXPERIMENTAL DESIGN: Patients received escalating doses of weekly docetaxel (days 1 and 8) and twice weekly bortezomib (days 2, 5, 9, and 12) in 3-week cycles. Two subjects were enrolled at each dose level, with cohort expansion to six for dose-limiting toxicity (DLT). Dose levels 1, 2, and 3 consisted of docetaxel/bortezomib 25/0.8, 25/1.0, and 30/1.0 mg/m(2), respectively. CYP3A activity and docetaxel pharmacokinetic studies were conducted, and proteasome inhibition was assessed. RESULTS: Fourteen patients received a total of 34 cycles of treatment. Dose level 2 was expanded for DLT that occurred in two of six patients consisting of febrile neutropenia in one patient and grade 3 thrombocytopenia in one patient. One patient received two cycles at dose level 3 with dose reduction to dose level 2, where grade 3 thrombocytopenia occurred at cycle 3. Both episodes of grade 3 thrombocytopenia were transient ( |
| Databáze: | OpenAIRE |
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