inhibiting beta-adrenergic and cox-2 signaling during the perioperative period to reduce ovarian cancer progression

Conditions: Ovarian Cancer; Ovarian Cancer Metastatic Recurrent

Summary: this study investigates the impact of perioperative inhibition of beta-adrenergic and cox-2 signaling in ovarian cancer patients undergoing debulking surgery. the trial aims to assess the feasibility, safety, and biological effects of a combination of propranolol and etodolac in reducing cancer metastasis and improving immune responses.

the study is a placebo-controlled randomized clinical trial (rct) enrolling 60 women undergoing ovarian cancer debulking surgery. participants will be assigned to receive propranolol (starting 5 days preoperatively, increased on the day of surgery, and continued postoperatively) and etodolac at a fixed dose. the primary outcomes include recruitment rate, drug safety, tolerability, adherence, and molecular tumor and blood characteristics. secondary outcomes include 3-year recurrence rates.

Eligibility criteria:
inclusion criteria: * age 20-85 * asa score 1-3 or ecog performance status of 0 to 2 * patients with a suspected high-grade ovarian epithelial cancer based on imaging, clinical examination, ca125, and/or tumor biopsy * patients planned for surgery for primary surgery, or interval debulking surgery for ovarian cancer * signed informed consent form * willing and able to comply with study procedures (physically and mentally) exclusion criteria: * patients who participate in another interventional study * patients with known allergy to one or more of the study medications, or to any medication from the non-steroidal anti-inflammatory drug group or beta-blockers family * patients treated chronically with any type of a beta-adrenergic blocker or a cox inhibitor, except use of aspirin, which will be discontinued at least 7 days prior to surgery, and until 3 weeks post-surgery * patients currently suffering from asthma (אסתמה פעילה בלבד), or required hospital admission or change in medical treatment for asthma within the past year * patients with active peptic disease * patients with a history of cva/tia * recent (within the last 5 years) or concurrent malignancies, with the exception of adequately treated in-situ carcinoma of the cervix or basal-cell carcinoma of the skin * patients with renal failure, measured by creatinine level \>1.5 * patients with significant liver dysfunction (known cirrhosis, bilirubin level\>2) * patients with significant heart failure (nyha functional class 3 or higher) * patients with bradycardia (heart rate of 50 or less) or second- or third-degree av block * patients with right-sided heart failure owing to pulmonary hypertension * patients with chronic digoxin treatment * patients with printzmetal's angina * patients with significant diagnosed cardiomegaly * patients suffering from sick sinus syndrome * patients with peripheral vascular disease * patients with current (unresected) pheochromocytoma * pregnant women * patients who are treated with immunosuppressive medications, including chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial drug * patients with immunodeficiency disorders

Keywords: ovarian cancer perioperative intervention beta-blockers propranolol cox-2 inhibitors etodolac psychoneuroimmunology stress and cancer randomized controlled trial (rct) biomarker analysis