A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer
| Autor: | Stephen T. C. Wong, Kartik Anand, Angel Rodriguez, Tejal Patel, Jenny C. Chang, Polly A. Niravath, Toniva Boone, Joe Ensor |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Adult Bridged-Ring Compounds Cancer Research medicine.medical_specialty Anthracycline medicine.medical_treatment Phases of clinical research Breast Neoplasms Disease-Free Survival Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols Medicine Humans Anthracyclines Aged Neoplasm Staging Chemotherapy Taxane Antibiotics Antineoplastic business.industry Ixabepilone Chloroquine Middle Aged medicine.disease Metastatic breast cancer 030104 developmental biology chemistry Docetaxel Drug Resistance Neoplasm 030220 oncology & carcinogenesis Female Taxoids business medicine.drug |
| Zdroj: | Clin Breast Cancer |
| ISSN: | 1938-0666 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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