Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression

Gynecol Oncol. 2019 Sep;154(3):524-530. doi: 10.1016/j.ygyno.2019.07.004. Epub 2019 Jul 25.

Abstract

Objective: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment.

Methods: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response.

Results: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response.

Conclusion: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.

Keywords: Adrenergic blockade; Beta blocker; IL 6; IL10; IL8; Ovarian cancer; Propranolol.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carboplatin / administration & dosage
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / immunology
  • Carcinoma, Ovarian Epithelial / surgery
  • Chemotherapy, Adjuvant
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / immunology
  • Feasibility Studies
  • Female
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Longitudinal Studies
  • Middle Aged
  • Neoadjuvant Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / surgery
  • Paclitaxel / administration & dosage
  • Pilot Projects
  • Propranolol / administration & dosage*
  • Prospective Studies
  • Quality of Life

Substances

  • Adrenergic beta-Antagonists
  • Cytokines
  • Propranolol
  • Carboplatin
  • Paclitaxel