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Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study.
- Source :
- British Journal of Cancer; 5/5/2008, Vol. 98 Issue 9, p1500-1507, 8p, 5 Charts, 1 Graph
- Publication Year :
- 2008
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- BREAST cancer
CANCER patients
NEUTROPENIA
ANTINEOPLASTIC agents
THERAPEUTICS
PHARMACOKINETICS
GLYCOPROTEINS
THERAPEUTIC use of antineoplastic agents
BALDNESS
ANTINEOPLASTIC antibiotics
RESEARCH
NAUSEA
DIARRHEA
ANTHRACYCLINES
CLINICAL trials
BORON compounds
HETEROCYCLIC compounds
RESEARCH methodology
EVALUATION research
MEDICAL cooperation
TREATMENT effectiveness
HYDROCARBONS
MALE breast cancer
DRUG administration
VOMITING
COMPARATIVE studies
BREAST tumors
LONGITUDINAL method
Subjects
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 98
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31876242
- Full Text :
- https://doi.org/10.1038/sj.bjc.6604347