Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study
| Autor: | Joan Albanell, Luc Dirix, Ahmad Awada, Pere Gascon, José Baselga, Thierry Gil, Martine Piccart, Peter Canney, Fatima Cardoso |
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| Rok vydání: | 2008 |
| Předmět: |
Oncology
Male Cancer Research Breast Neoplasms Male -- pathology Docetaxel Antineoplastic Combined Chemotherapy Protocols -- adverse effects Taxoids -- administration & dosage Anthracyclines -- administration & dosage Bortezomib Breast cancer Belgium hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols Clinical Studies Proteasome inhibitor Anthracyclines Prospective Studies Breast Neoplasms Male -- drug therapy Antibiotics Antineoplastic Pyrazines -- administration & dosage Great Britain Nausea Sciences bio-médicales et agricoles Middle Aged Metastatic breast cancer Boronic Acids metastatic Treatment Outcome Pyrazines anthracycline-pretreated Boronic Acids -- administration & dosage Breast Neoplasms -- pathology Metastatic Female Taxoids medicine.drug Adult Diarrhea medicine.medical_specialty Neutropenia Anthracycline Vomiting Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics Nausea -- chemically induced Anthracycline-pretreated Breast Neoplasms -- drug therapy Breast Neoplasms Antineoplastic Combined Chemotherapy Protocols -- therapeutic use Neutropenia -- chemically induced Drug Administration Schedule Breast Neoplasms Male breast cancer Internal medicine medicine Humans neoplasms Aged Vomiting -- chemically induced business.industry proteasome inhibitor Alopecia Antibiotics Antineoplastic -- administration & dosage medicine.disease United Kingdom Surgery Alopecia -- chemically induced Spain Antineoplastic Combined Chemotherapy Protocols -- administration & dosage business Febrile neutropenia Diarrhea -- chemically induced |
| Zdroj: | British Journal of Cancer British Journal of Cancer, 98 (9 |
| ISSN: | 1532-1827 |
| Popis: | The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60-100 mg m(-2) on day 1) plus bortezomib (1.0-1.5 mg m(-2) on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m(-2) plus docetaxel 75 mg m(-2). All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents. Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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