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


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).


CONCLUSIONS
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.
Yang
C H
CH
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gonzalez-Angulo
A M
AM
Reuben
J M
JM
Booser
D J
DJ
Pusztai
L
L
Krishnamurthy
S
S
Esseltine
D
D
Stec
J
J
Broglio
K R
KR
Islam
R
R
Hortobagyi
G N
GN
Cristofanilli
M
M
D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000069286:Bortezomib