Annals of Oncology Advance Access published online on January 10, 2006
Annals of Oncology, doi:10.1093/annonc/mdj131
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1 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
* To whom correspondence should be addressed. Background: Bortezomib (VELCADE®) is a potent inhibitor of the 26S proteasome with broad antitumor activity. We performed a phase II study of bortezomib to evaluate its clinical effects in patients with metastatic breast cancer. Patients and methods: Twelve patients with metastatic breast cancer were treated with bortezomib (VELCADE®) at a dosage of 1.5 mg/m2 administered biweekly for 2 weeks with 1 week of rest in a 21-day cycle. The primary objective was clinical response rate. Toxicity and pharmacodynamics data were also obtained. Results: No objective responses were observed. One patient had stable disease, and 11 others experienced disease progression. The median survival time was 4.3 months (range, 0.9-37 months). The most common grade 3 or 4 toxicities included fatigue (58%; n = 7) and skin rash (33%; n = 4). The mean inhibition of specific chymotryptic activity was 53.1% (± 13.33%). A statistically significant reduction in the plasma interleukin-6 level was seen (P = 0.0354). Conclusion: Bortezomib was well tolerated but showed limited clinical activity against metastatic breast cancer when used as a single agent. The future development of this agent for the treatment of breast cancer should be guided by in vivo models that optimize activity in combination with other antitumor agents.
Received November 7, 2005
Revised November 24, 2005
Accepted December 2, 2005
original article
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
C. H. Yang 1,
A. M. Gonzalez-Angulo 1,
J. M. Reuben 2,
D. J. Booser 1,
L. Pusztai 1,
S. Krishnamurthy 3,
D. Esseltine 4,
J. Stec 4,
K. R. Broglio 5,
R. Islam 1,
G. N. Hortobagyi 1,
and
M. Cristofanilli 1 *
2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Millennium Pharmaceuticals Inc., Cambridge MA, USA
5 Department of Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
M. Cristofanilli, E-mail: mcristof{at}mdanderson.orgb
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