A Clinical Trial of the P-Glycoprotein Antagonist, Tariquidar (XR9576), in Combination With Docetaxel in Patients With Lung, Ovarian, Renal and Cervical Cancer: Analysis of the Interaction Between Tariquidar and Docetaxel
Intrinsic and acquired drug resistance remain major obstacles in the treatment of cancer.
Accumulating evidence indicates that in some malignancies P-glycoprotein (Pgp) can confer
resistance, and that its reversal can improve therapeutic outcome. Clinical trials
investigating Pgp antagonists have been hampered by the occurrence of unpredictable
pharmacokinetic interactions, which have required dose reductions of the chemotherapeutic
agents to avert excessive toxicity. Tariquidar (XR9576) is a new Pgp antagonist that is more
potent and has prolonged activity. Phase I trials with paclitaxel, vinorelbine, and
docetaxel have demonstrated that tariquidar (XR9576) has minimal pharmacokinetic
interactions while surrogate studies have confirmed in vivo inhibition of Pgp-mediated drug
transport.This study seeks to determine the pharmacokinetic interaction, if any between
docetaxel and tariquidar and to evaluate the potential for activity in lung, ovarian,
primary peritoneal, fallopian tube and cervical cancers. Renal cell cancer has been added in
a 3/1/06 amendment. The secondary goal is to evaluate the impact of tariquidar on uptake of
(99m)Tc-sestamibi in recurrent or metastatic tumors of patients with lung, ovarian, renal or
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Geometric Mean of Maximum Concentration of the Drug (Cmax)
In the first cycle patients were to receive docetaxel on days 1 and 8 and to be randomized to receive tariquidar on either day 1 or 8. Thus pharmacokinetic data with and without tariquidar can be compared.
Susan E Bates, M.D.
United States: Federal Government
|National Institutes of Health||Bethesda, Maryland 20892|