Phase II study of propranolol feasibility with neoadjuvant chemotherapy in patients with newly diagnosed breast cancer.

PURPOSE: Propranolol regulates angiogenesis in pre-clinical models and reduces distant breast cancer (BC) metastases in observational studies. We assessed the feasibility of combining propranolol with neoadjuvant chemotherapy (NAC) in patients with BC.

METHODS: Women with clinical stage II-III BC undergoing NAC [weekly paclitaxel × 12, followed by dose-dense adriamycin/cyclophosphamide (AC) × 4] started propranolol 20 mg PO BID with paclitaxel #1, and increased to 80 mg extended release (ER) PO daily, as tolerated. The primary endpoint was to assess feasibility, defined as at least 75% of patients having at least 80% adherence to propranolol as prescribed. Secondary endpoints included identifying safety, rate of dose holds and modification, and rate of reaching 80 mg ER daily. The proposed sample size was 20 patients.

RESULTS: From November 2012 to September 2015, ten patients were enrolled. Median age was 50.5 years (range, 44-67). All patients had hormone receptor-positive/HER2-negative breast cancer. Three women had grade I bradycardia that resulted in a 1-week delay in increasing the propranolol dose. Ninety percent of women reached the target propranolol dosing of 80 mg ER daily, and 70% took the target propranolol dose until the night before surgery. Of the 4 women who dose-reduced propranolol, 1 increased to the target propranolol dose. Mean adherence to propranolol dosing was 96% (range: 91-100%). All patients went to surgery.

CONCLUSION: Our results support the feasibility of combining propranolol (up to 80 mg ER) with neoadjuvant taxane/anthracycline-based chemotherapy.