Bortezomib (VELCADE®) in metastatic breast cancer: Pharmacodynamics, biological effects, and prediction of clinical benefits

C. H. Yang, A. M. Gonzalez-Angulo, J. M. Reuben, D. J. Booser, L. Pusztai, S. Krishnamurthy, D. Esseltine, J. Stec, K. R. Broglio, R. Islam, G. N. Hortobagyi, M. Cristofanilli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)813-817
Number of pages5
JournalAnnals of Oncology
Volume17
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Bortezomib
  • Breast cancer
  • Proteasome inhibitor
  • Velcade

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Bortezomib (VELCADE®) in metastatic breast cancer: Pharmacodynamics, biological effects, and prediction of clinical benefits'. Together they form a unique fingerprint.

Cite this