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

Lois M. Ramondetta, Wei Hu, Premal H. Thaker, Diana L. Urbauer, Gary B. Chisholm, Shannon N. Westin, Yunjie Sun, Pedro T. Ramirez, Nicole Fleming, Sunil K. Sahai, Alpa M. Nick, Jesusa M.G. Arevalo, Thomas Dizon, Robert L. Coleman, Steve W. Cole, Anil K. Sood

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)524-530
Number of pages7
JournalGynecologic oncology
Volume154
Issue number3
DOIs
StatePublished - Sep 2019

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Propranolol
Gene Expression
Drug Therapy
Adrenergic Agents
Therapeutics
Combination Drug Therapy
Interleukin-8
Interleukin-10
Interleukin-6
Leukocytes
Anxiety
Ovarian epithelial cancer
Depression
Serum
Genes

Keywords

  • Adrenergic blockade
  • Beta blocker
  • IL 6
  • IL10
  • IL8
  • Ovarian cancer
  • Propranolol

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression. / Ramondetta, Lois M.; Hu, Wei; Thaker, Premal H.; Urbauer, Diana L.; Chisholm, Gary B.; Westin, Shannon N.; Sun, Yunjie; Ramirez, Pedro T.; Fleming, Nicole; Sahai, Sunil K.; Nick, Alpa M.; Arevalo, Jesusa M.G.; Dizon, Thomas; Coleman, Robert L.; Cole, Steve W.; Sood, Anil K.

In: Gynecologic oncology, Vol. 154, No. 3, 09.2019, p. 524-530.

Research output: Contribution to journalArticle

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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",
author = "Ramondetta, {Lois M.} and Wei Hu and Thaker, {Premal H.} and Urbauer, {Diana L.} and Chisholm, {Gary B.} and Westin, {Shannon N.} and Yunjie Sun and Ramirez, {Pedro T.} and Nicole Fleming and Sahai, {Sunil K.} and Nick, {Alpa M.} and Arevalo, {Jesusa M.G.} and Thomas Dizon and Coleman, {Robert L.} and Cole, {Steve W.} and Sood, {Anil K.}",
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T1 - Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression

AU - Ramondetta, Lois M.

AU - Hu, Wei

AU - Thaker, Premal H.

AU - Urbauer, Diana L.

AU - Chisholm, Gary B.

AU - Westin, Shannon N.

AU - Sun, Yunjie

AU - Ramirez, Pedro T.

AU - Fleming, Nicole

AU - Sahai, Sunil K.

AU - Nick, Alpa M.

AU - Arevalo, Jesusa M.G.

AU - Dizon, Thomas

AU - Coleman, Robert L.

AU - Cole, Steve W.

AU - Sood, Anil K.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Adrenergic blockade

KW - Beta blocker

KW - IL 6

KW - IL10

KW - IL8

KW - Ovarian cancer

KW - Propranolol

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