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Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma
Author(s) -
Pusztai Lajos,
Wagner Peter,
Ibrahim Nuhad,
Rivera Edgardo,
Theriault Richard,
Booser Daniel,
Symmans Fraser W.,
Wong Franklin,
Blumenschein George,
Fleming Donald R.,
Rouzier Roman,
Boniface Graeme,
Hortobagyi Gabriel N.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21227
Subject(s) - medicine , chemotherapy , oncology , breast carcinoma , phases of clinical research , breast cancer , cancer
BACKGROUND The primary objective of this study was to determine whether addition of the selective P‐glycoprotein (P‐gp) inhibitor tariquidar (XR9576) to chemotherapy could induce an objective tumor response in patients who previously were resistant to the same agents. The secondary objectives were to evaluate P‐gp expression by immunohistochemistry (IHC), to determine functional activity of the P‐gp transporter before and after administration of tariquidar with serial technetium‐99m ( 99m Tc)‐sestamibi scans, and to correlate those parameters with clinical response. METHODS Seventeen women with Stage III–IV breast carcinoma were included in the study who progressed ( n = 13 women) or had stable disease ( n = 4 women) on doxorubicin‐containing or taxane‐containing chemotherapy regimens. During the study, the same chemotherapy was continued without dose modifications, but tariquidar (150 mg intravenously) was added to the treatment regimen. RESULTS Thirty‐six percent of patients had P‐gp‐positive tumors by IHC, and 5 patients (29%) experienced increases ≥ 10% in sestamibi uptake (median increase, 40%; range, 10–63%) after the administration of tariquidar. There was one partial response in a patient who had the greatest increase in sestamibi uptake and who also showed inducible P‐gp expression. There was one patient who experienced severe doxorubicin/docetaxel‐related toxicity after tariquidar was added to her chemotherapy regimen. CONCLUSIONS Tariquidar showed limited clinical activity to restore sensitivity to anthracycline or taxane chemotherapy. Functional imaging of the tumor with 99m Tc‐sestamibi scans before and after administration of multidrug‐resistance inhibitor may be useful to identify the small subset of patients who could benefit from multidrug‐resistance modulation in future trials. Cancer 2005. © 2005 American Cancer Society.