TY - JOUR
T1 - Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer
AU - Irvin, William J.
AU - Orlowski, Robert Z.
AU - Chiu, Wing Keung
AU - Carey, Lisa A.
AU - Collichio, Frances A.
AU - Bernard, Philip S.
AU - Stijleman, Inge J.
AU - Perou, Charles
AU - Ivanova, Anastasia
AU - Dees, E. Claire
N1 - Funding Information:
This study was supported in part by grants from Ortho Biotech Products, L.P., Millennium Pharmaceuticals, Inc., the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health (RR00046), and the National Cancer Institute SPORE in Breast Cancer (5-P50-CA58223).
PY - 2010/12
Y1 - 2010/12
N2 - Background: Based on preclinical studies and a phase I trial of the combination of bortezomib and pegylated liposomal doxorubicin (PLD), which both showed activity in breast cancer, we conducted a phase II study of this regimen in patients with metastatic breast cancer. Patients and Methods: Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle, along with PLD 30 mg/m2 on day 4. The primary objective was to evaluate the response rate of this combination, while secondary objectives were to obtain further safety data about this combination, to evaluate the time to disease progression (TTP), and to evaluate response by the breast cancer subtype. Results: One of 12 evaluable patients had a partial response (8%), while 3 (25%) had stable disease. At 26 months follow-up, the median overall survival was 4.3 months (95% CI, 1.2-26.2) and the median TTP was 1.3 months (95% CI, 0.8-14.0 months). The combination was well tolerated, with the most common events including low-grade nausea and vomiting, neutropenia, and neuropathy, and no cardiac toxicity was seen. Of the 7 tumors subtyped, no association was seen between intrinsic subtype or receptor status and response. Conclusion: The combination of PLD and bortezomib was well tolerated but has minimal activity in heavily pretreated unselected metastatic breast cancer.
AB - Background: Based on preclinical studies and a phase I trial of the combination of bortezomib and pegylated liposomal doxorubicin (PLD), which both showed activity in breast cancer, we conducted a phase II study of this regimen in patients with metastatic breast cancer. Patients and Methods: Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle, along with PLD 30 mg/m2 on day 4. The primary objective was to evaluate the response rate of this combination, while secondary objectives were to obtain further safety data about this combination, to evaluate the time to disease progression (TTP), and to evaluate response by the breast cancer subtype. Results: One of 12 evaluable patients had a partial response (8%), while 3 (25%) had stable disease. At 26 months follow-up, the median overall survival was 4.3 months (95% CI, 1.2-26.2) and the median TTP was 1.3 months (95% CI, 0.8-14.0 months). The combination was well tolerated, with the most common events including low-grade nausea and vomiting, neutropenia, and neuropathy, and no cardiac toxicity was seen. Of the 7 tumors subtyped, no association was seen between intrinsic subtype or receptor status and response. Conclusion: The combination of PLD and bortezomib was well tolerated but has minimal activity in heavily pretreated unselected metastatic breast cancer.
KW - Dexamethasone
KW - Liver metastases
KW - Ondansetron
KW - Proteasome inhibitor
KW - Pyridoxine
KW - Ranitidine
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U2 - 10.3816/CBC.2010.n.061
DO - 10.3816/CBC.2010.n.061
M3 - Article
C2 - 21147690
AN - SCOPUS:79952277119
SN - 1526-8209
VL - 10
SP - 465
EP - 470
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 6
ER -