A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients
Chloroquine has demonstrated anti-tumor activities through autophagy inhibition and cell cycle disruption. This study aimed to assess the effect of single-agent chloroquine on breast tumor cellular proliferation in a randomized, phase II, double-blind, placebo-controlled, pre-surgical window of opportunity trial.
Patients with newly diagnosed breast cancer were randomized 2:1 to chloroquine 500 mg daily or placebo for 2- to 6-weeks prior to their breast surgery. The primary outcome was the relative change in measures of proliferation (Ki67) in primary breast cancer cells pre- and post-treatment. Adverse events and toxicity profiles were also evaluated.
From September 2015 to December 2016, 70 patients were randomized [46 (66%) chloroquine and 24 (34%) placebo]. Ten patients who were randomized to chloroquine withdrew from study due to adverse events. Mean duration of drug intake was 15 days (range 14–29 days). There were no significant differences between the chloroquine or placebo arms with respect to either the percentage change (− 0.4 vs. − 1.2, p = 0.088) or absolute change (− 2.0% vs. − 5.2%, p = 0.066) in Ki67 index pre- and post-drug treatment. Although adverse effects were minimal and all classified as grade 1, the effects were significant enough to cause nearly 15% of patients to discontinue therapy.
Treatment with single-agent chloroquine 500 mg daily in the preoperative setting was not associated with any significant effects on breast cancer cellular proliferation. It was, however, associated with toxicity that may affect its broader use in oncology.
KeywordsWindow of opportunity clinical trial Chloroquine Breast cancer
The authors are grateful to the research staff for their assistance in recruiting participants and for data collection.
This trial was supported by the Canadian Breast Cancer Foundation Ontario Chapter and University of Ottawa Department of Surgery research Grant.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ottawa Hospital Research Ethics Board) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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