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

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/m(2) 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.

• Authors: 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 5 Pg. 813-7 (May 2006) ISSN: 0923-7534 [Print] England
• PMID: 16403809 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Boronic Acids
• Protease Inhibitors
• Pyrazines
• Receptors, Estrogen
• Receptors, Progesterone
• Bortezomib

Topics

• Adult
• Aged
• Bone Neoplasms (drug therapy, secondary)
• Boronic Acids (pharmacology, therapeutic use)
• Bortezomib
• Breast Neoplasms (drug therapy, pathology)
• Disease Progression
• Disease-Free Survival
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pleural Neoplasms (drug therapy, secondary)
• Protease Inhibitors (pharmacology, therapeutic use)
• Pyrazines (pharmacology, therapeutic use)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Soft Tissue Neoplasms (drug therapy, secondary)
• Survival Rate
• Treatment Outcome