Phase II study of tariquidar, a selective P-glycoprotein inhibitor, in patients with chemotherapy-resistant, advanced breast carcinoma

Cancer. 2005 Aug 15;104(4):682-91. doi: 10.1002/cncr.21227.


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 > or = 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Immunohistochemistry
  • Infusions, Intravenous
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / drug therapy*
  • Quinolines / administration & dosage
  • Quinolines / adverse effects*
  • Technetium Tc 99m Sestamibi
  • Tomography, Emission-Computed


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Quinolines
  • Technetium Tc 99m Sestamibi
  • tariquidar