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Sponsors and Collaborators: |
Hadassah Medical Organization Tel Aviv University |
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Information provided by: | Hadassah Medical Organization |
ClinicalTrials.gov Identifier: | NCT00502684 |
Surgery for breast cancer has a major role in enhancing long term survival and cure, but several physiological aspects associated with surgery are implicated as enhancing tumor spread and formation of distant metastases.
These include: an increase in pro-angiogenic factors, direct spread of tumor cells, accumulation of grown factors, immune suppression and direct effects of anesthetics and opiate pain relievers on cancer cells. Some of these pro-metastatic mechanism may be blocked by the interventions proposed in this study, namely by administration of β-adrenergic blockers and COX2 inhibitors around the time of surgery.
Studies have shown that surgery increases levels of catecholamines and prostaglandins, which in turn may promote the release of pro-angiogenic factors such as VEGF, and enhance vascularization of micro metastases.
Opiates given for pain relief during and after surgery have been reported to enhance tumor cell division and cause immune suppression. The immune system is significantly suppressed during surgery. This suppression has been shown to affect the systemic resistance to infection as well as neoplastic metastatic processes. Several studies have shown that increased levels of catecholamines and prostaglandins add to the immune suppression. Studies in rats found that peri-operative administration of the beta β-blocker propranolol together with the COX2 inhibitor etodolac significantly reduced the suppression of NK cell activity as well as the risk for distant metastases. A recent retrospective clinical study found that among breast cancer patients treated with a combination of regional anesthesia and a COX inhibitor the recurrence rated were significantly less than among patients undergoing surgery without these two interventions. The purpose of the proposed prospective trial is to examine if peri-operative administration of the combination of a β-blocker together with a COX2 inhibitor will prevent suppression of cellular immunity, decrease VEGF levels, and decrease cancer recurrence rates. In the proposed study breast cancer patients will be treated with a combination of a β-blocker and COX2 inhibitor (or placebo) before, during and after surgery. (A control group of healthy women will serve as untreated controls). The variables which will be examined are: number and activity of NK cells, levels of Th1 and Th2 cytokines, serum stress hormones and angiogenic factors, and the ability of leukocytes to produce Th1 and Th2 cytokines as a result of in vitro stimulation. In addition to these immediate parameters, long term follow up will be conducted in order to determine the effect of the intervention on long term cancer recurrence over five years. Statistical analysis will be done using t-tests, ANOVA, and multivariate regressions, with regard to the known risk factors for recurrence such as tumor grade, lymph node involvement etc. Sample size for immunological parameters will be 40 patients in each group and 20 healthy women. Sample size for estimates of cancer recurrence at five years of follow up wiil be 460 women (230 in each group). This sample size provides a power of 80% to detect a 50% reduction in cancer recurrence at an α of 0.05.
Condition | Intervention |
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Primary Operable Breast Cancer |
Drug: Propranolol, etodolac |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment |
Official Title: | Perioperative Administration of COX 2 Inhibitors and Beta Blockers in Women Undergoing Breast Cancer Surgery: an Intervention to Decrease Immune Suppression, Metastatic Potential and Cancer Recurrence |
Estimated Enrollment: | 460 |
Study Start Date: | October 2007 |
Ages Eligible for Study: | 20 Years to 75 Years |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Women scheduled to undergo surgery for primary breast cancer.
Exclusion Criteria:
• Patients with renal failure (creatinin >1.5)
Contact: Tanir M Allweis, MD | +972-2-584-4111 ext 74268 | tanir@hadassah.org.il |
Israel | |
Hadassah Hebrew University MEdical Center | |
Jerusalem, Israel, 91120 |
Principal Investigator: | Tanir M Allweis, MD | Hadassah-Hebrew University Medical Center |
Study Director: | Shamgar Ben-Eliyahu, PhD | Tel Aviv University, Neuroimmunology Research Unit |
Study ID Numbers: | 392-22.6.07 / 2358 |
Study First Received: | July 17, 2007 |
Last Updated: | September 19, 2007 |
ClinicalTrials.gov Identifier: | NCT00502684 History of Changes |
Health Authority: | Israel: Ministry of Health |
breast cancer surgery immune suppression beta blockers COX2 inhibitors |
Anti-Inflammatory Agents Vasodilator Agents Neurotransmitter Agents Skin Diseases Adrenergic Agents Cyclooxygenase Inhibitors Breast Neoplasms Cardiovascular Agents Antihypertensive Agents Cyclooxygenase 2 Inhibitors Recurrence |
Propranolol Analgesics, Non-Narcotic Etodolac Adrenergic beta-Antagonists Anti-Inflammatory Agents, Non-Steroidal Adrenergic Antagonists Peripheral Nervous System Agents Analgesics Anti-Arrhythmia Agents Breast Diseases |
Anti-Inflammatory Agents Neurotransmitter Agents Vasodilator Agents Molecular Mechanisms of Pharmacological Action Adrenergic Agents Physiological Effects of Drugs Cyclooxygenase 2 Inhibitors Neoplasms by Site Propranolol Sensory System Agents Therapeutic Uses Adrenergic beta-Antagonists Anti-Inflammatory Agents, Non-Steroidal Anti-Arrhythmia Agents |
Analgesics Breast Diseases Skin Diseases Cyclooxygenase Inhibitors Breast Neoplasms Enzyme Inhibitors Cardiovascular Agents Antihypertensive Agents Pharmacologic Actions Neoplasms Analgesics, Non-Narcotic Adrenergic Antagonists Peripheral Nervous System Agents |