期刊
CLINICAL BREAST CANCER
卷 21, 期 3, 页码 199-204出版社
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clbc.2020.09.015
关键词
Cancer stem cells; Choloroquine; Docetaxel; Ixabepilone; Triple negative breast cancer
类别
资金
- Breast Cancer Research Foundation
- CREDO
- T.T. & W.F. Chao Foundation
- John S Dunn. Research Foundation
- National Institutes of Health [U54 CA210181, U54 CA149196]
The combination of chloroquine with taxane or taxane-like chemotherapy was effective in patients with locally advanced or metastatic breast cancer, achieving an overall response rate of 45%, higher than the expected 30%.
Chemotherapy eliminates most cancer cells except cancer stem cells. Chloroquine is a potential agent to target cancer stem cells. In this phase II trial for patients with breast cancer who were refractory to anthracycline-based chemotherapy, we combined chloroquine with taxane or taxane-like chemotherapy. The overall response rate of the combination was 45%, higher than the expected overall response rate of 30% with chemotherapy alone. Introduction: Chemotherapy eliminates most of the cancer cells except those with potential for self-renewal and tumor initiation, called cancer stem cells (CSCs). Chloroquine, through bioinformatics, was found to be a potential agent to target CSCs. We designed a phase II trial to test the efficacy and safety of chloroquine in combination with taxane or taxane-like chemotherapy agents in patients with advanced or metastatic breast cancer who are refractory to anthracycline-based chemotherapy. Patients and Methods: Female patients >= 18 years of age who had received prior anthracycline chemotherapy were enrolled in this study. Chloroquine 250 mg was given daily orally with either docetaxel or paclitaxel or nab-paclitaxel or ixabepilone every 3 weeks. The maximum number of 3-week cycles allowed was 6. The primary efficacy endpoint was the objective response rate (ORR). The secondary efficacy endpoints included progression-free survival (PFS) and safety analysis. Results: Thirty-eight patients were enrolled in the study, and 31 patients were evaluated for response. The median age was 54.1 years (range, 31.7-78.1 years). The ORR was 45.16% (95% confidence interval [CI], 29.2%-62.2%), which was higher than the expected ORR of 30% (P = .03). Patients were followed for a median of 25.4 months and experienced a median PFS of 12.4 months (95% CI, 4.9-24.6 months) and a median OS of 25.4 months (95% CI, 13.7-83.5 months). The combination was well-tolerated, with only 13.15% of patients experiencing grade > 3 adverse events. Conclusion: A combination of chloroquine with taxane or taxane-like chemotherapy was efficacious in patients with locally advanced or metastatic breast cancer with prior anthracycline-based chemotherapy. (C) 2020 Published by Elsevier Inc.
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