Annals of Oncology Advance Access originally published online on January 10, 2006
Annals of Oncology 2006 17(5):813-817; doi:10.1093/annonc/mdj131
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© 2006 European Society for Medical Oncology
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
1 Departments of Breast Medical Oncology, 2 Hematopathology, 3 Pathology, 5 Biostatistics and Applied Mathematics, The University of Texas MD Anderson Cancer Center, Houston, TX; 4 Millennium Pharmaceuticals Inc., Cambridge MA, USA
* Correspondence to: Dr M. Cristofanilli, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1354, Houston, TX 77030, USA Tel: +1 713 792 2817; Fax: +1 713 794 4385. E-mail: mcristof{at}mdanderson.orgb
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.
Key words: bortezomib, Velcade, breast cancer, proteasome inhibitor
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