Madeleine B Hopson1, Shing Lee2,3, Melissa Accordino1,3, Meghna Trivedi1,3, Matthew Maurer4, Katherine D Crew1,2,3, Dawn L Hershman1,2,3, Kevin Kalinsky5. 1. Columbia University Irving Medical Center, 630 W 168th St, New York, NY, 10032, USA. 2. Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA. 3. Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA. 4. Bristol-Myers Squibb, 100 Nassau Park Blvd #300, Princeton, NJ, 08540, USA. 5. Winship Cancer Institute at Emory University, 1365 Clifton Road, Suite B4112, Atlanta, GA, 30322, USA. kkalins@emory.edu.
Abstract
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.
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.
Entities:
Keywords:
Angiogenesis; Breast Cancer; Neoadjuvant chemotherapy; Propranolol
Authors: Patrick A Oberholzer; Damien Kee; Piotr Dziunycz; Antje Sucker; Nyam Kamsukom; Robert Jones; Christine Roden; Clinton J Chalk; Kristin Ardlie; Emanuele Palescandolo; Adriano Piris; Laura E MacConaill; Caroline Robert; Günther F L Hofbauer; Grant A McArthur; Dirk Schadendorf; Levi A Garraway Journal: J Clin Oncol Date: 2011-11-07 Impact factor: 44.544
Authors: Xavier Pivot; Andreas Schneeweiss; Shailendra Verma; Christoph Thomssen; José Luis Passos-Coelho; Giovanni Benedetti; Eva Ciruelos; Roger von Moos; Hong-Tai Chang; Anja-Alexandra Duenne; David W Miles Journal: Eur J Cancer Date: 2011-07-15 Impact factor: 9.162
Authors: Erica K Sloan; Saul J Priceman; Benjamin F Cox; Stephanie Yu; Matthew A Pimentel; Veera Tangkanangnukul; Jesusa M G Arevalo; Kouki Morizono; Breanne D W Karanikolas; Lily Wu; Anil K Sood; Steven W Cole Journal: Cancer Res Date: 2010-09-07 Impact factor: 12.701
Authors: Patricia A Ganz; Laurel A Habel; Erin K Weltzien; Bette J Caan; Steven W Cole Journal: Breast Cancer Res Treat Date: 2011-04-11 Impact factor: 4.872
Authors: Premal H Thaker; Liz Y Han; Aparna A Kamat; Jesusa M Arevalo; Rie Takahashi; Chunhua Lu; Nicholas B Jennings; Guillermo Armaiz-Pena; James A Bankson; Murali Ravoori; William M Merritt; Yvonne G Lin; Lingegowda S Mangala; Tae Jin Kim; Robert L Coleman; Charles N Landen; Yang Li; Edward Felix; Angela M Sanguino; Robert A Newman; Mary Lloyd; David M Gershenson; Vikas Kundra; Gabriel Lopez-Berestein; Susan K Lutgendorf; Steven W Cole; Anil K Sood Journal: Nat Med Date: 2006-07-23 Impact factor: 53.440
Authors: N Weidner; J Folkman; F Pozza; P Bevilacqua; E N Allred; D H Moore; S Meli; G Gasparini Journal: J Natl Cancer Inst Date: 1992-12-16 Impact factor: 13.506
Authors: Aeson Chang; Erica K Sloan; Michael H Antoni; Jennifer M Knight; Rachel Telles; Susan K Lutgendorf Journal: Integr Cancer Ther Date: 2022 Jan-Dec Impact factor: 3.077
Authors: Virginia Albiñana; Eunate Gallardo-Vara; Juan Casado-Vela; Lucía Recio-Poveda; Luisa María Botella; Angel M Cuesta Journal: J Clin Med Date: 2022-08-04 Impact factor: 4.964