BACKGROUND: Blockade of platelet activation and aggregation can inhibit metastasis in preclinical models and is associated with cancer prevention. To test whether disruption of platelet function with clopidogrel and aspirin would decrease the number of circulating tumor cells (CTCs) in patients with metastatic breast cancer, a randomized phase II study was performed. METHODS:Patients with metastatic breast cancer who were not currently receivingcytotoxic chemotherapy were eligible. Patients were randomized to receive either clopidogrel and aspirin or to a control group receiving no treatment. Phlebotomy was performed at baseline, at 2 and 4 weeks, and monthly thereafter to obtain specimens to assess CTC, platelet aggregation, and thrombin activity. The primary end point was the proportion of patients with detectable CTCs at 1 month. RESULTS:Forty-eight patients were enrolled and 42 were evaluable at 1 month. Baseline CTC numbers were ≥ 5 in 13% and ≥ 1 in 65% of patients. Despite adequate platelet function inhibition in the treatment group, the proportion of patients with detectable CTCs was similar between the clopidogrel/aspirin and control groups at baseline (P = .21) and 4 weeks (P = .75), showing no treatment effect. Measured endogenous thrombin potential did not correlate with CTC number. No bleeding-related serious adverse events (SAEs) occurred. CONCLUSION: The baseline CTC numbers were lower than expected, decreasing the ability to detect an impact of platelet inhibition on CTCs. Clopidogrel and aspirin were well tolerated. Future studies evaluating the potential therapeutic role of antiplatelet therapy in breast cancer remain of interest, and they may be informed by these results.
RCT Entities:
BACKGROUND: Blockade of platelet activation and aggregation can inhibit metastasis in preclinical models and is associated with cancer prevention. To test whether disruption of platelet function with clopidogrel and aspirin would decrease the number of circulating tumor cells (CTCs) in patients with metastatic breast cancer, a randomized phase II study was performed. METHODS:Patients with metastatic breast cancer who were not currently receiving cytotoxic chemotherapy were eligible. Patients were randomized to receive either clopidogrel and aspirin or to a control group receiving no treatment. Phlebotomy was performed at baseline, at 2 and 4 weeks, and monthly thereafter to obtain specimens to assess CTC, platelet aggregation, and thrombin activity. The primary end point was the proportion of patients with detectable CTCs at 1 month. RESULTS: Forty-eight patients were enrolled and 42 were evaluable at 1 month. Baseline CTC numbers were ≥ 5 in 13% and ≥ 1 in 65% of patients. Despite adequate platelet function inhibition in the treatment group, the proportion of patients with detectable CTCs was similar between the clopidogrel/aspirin and control groups at baseline (P = .21) and 4 weeks (P = .75), showing no treatment effect. Measured endogenous thrombin potential did not correlate with CTC number. No bleeding-related serious adverse events (SAEs) occurred. CONCLUSION: The baseline CTC numbers were lower than expected, decreasing the ability to detect an impact of platelet inhibition on CTCs. Clopidogrel and aspirin were well tolerated. Future studies evaluating the potential therapeutic role of antiplatelet therapy in breast cancer remain of interest, and they may be informed by these results.
Authors: W Jeffrey Allard; Jeri Matera; M Craig Miller; Madeline Repollet; Mark C Connelly; Chandra Rao; Arjan G J Tibbe; Jonathan W Uhr; Leon W M M Terstappen Journal: Clin Cancer Res Date: 2004-10-15 Impact factor: 12.531
Authors: Massimo Cristofanilli; G Thomas Budd; Matthew J Ellis; Alison Stopeck; Jeri Matera; M Craig Miller; James M Reuben; Gerald V Doyle; W Jeffrey Allard; Leon W M M Terstappen; Daniel F Hayes Journal: N Engl J Med Date: 2004-08-19 Impact factor: 91.245
Authors: H Coenraad Hemker; Peter Giesen; Raed Al Dieri; Véronique Regnault; Eric de Smedt; Rob Wagenvoord; Thomas Lecompte; Suzette Béguin Journal: Pathophysiol Haemost Thromb Date: 2003
Authors: Suzanne J Bakewell; Patrick Nestor; Srinivasa Prasad; Michael H Tomasson; Nikki Dowland; Mukund Mehrotra; Robert Scarborough; James Kanter; Keith Abe; David Phillips; Katherine N Weilbaecher Journal: Proc Natl Acad Sci U S A Date: 2003-11-11 Impact factor: 11.205
Authors: Bas Franken; Marco R de Groot; Walter J B Mastboom; Istvan Vermes; Job van der Palen; Arjan G J Tibbe; Leon W M M Terstappen Journal: Breast Cancer Res Date: 2012-10-22 Impact factor: 6.466
Authors: Jill M Pulley; Rebecca N Jerome; Martin L Ogletree; Gordon R Bernard; Robert R Lavieri; Nicole M Zaleski; Charles C Hong; Jana K Shirey-Rice; Carlos L Arteaga; Ingrid A Mayer; Kenneth J Holroyd; Rebecca S Cook Journal: Target Oncol Date: 2018-02 Impact factor: 4.493
Authors: L Yang; Z Lv; W Xia; W Zhang; Y Xin; H Yuan; Y Chen; X Hu; Y Lv; Q Xu; X Weng; C Ni Journal: Clin Transl Oncol Date: 2017-12-14 Impact factor: 3.405
Authors: Marek Z Wojtukiewicz; Dominika Hempel; Ewa Sierko; Stephanie C Tucker; Kenneth V Honn Journal: Cancer Metastasis Rev Date: 2017-06 Impact factor: 9.264
Authors: Preeti Kanikarla-Marie; Michael Lam; Alexey V Sorokin; Michael J Overman; Scott Kopetz; David G Menter Journal: Front Oncol Date: 2018-04-20 Impact factor: 6.244