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Sheba Study Indicates Readily-Available Drugs May Prevent Metastasis in Colon and Rectal Cancer Patients

Colon and Rectal Cancer patients post surgery stress-inflammatory response reduced with propranolol and etodolac.
A new clinical study of colon and rectal cancer patients carried out at Sheba found that treatment with propranolol (Deralin) and etodolac (Etopan) following the surgical removal of a tumor may prevent metastasis in the long term.

Favorable responses to the treatment were noted by Prof. Shamgar Ben-Eliyahu, a neuroscientist specializing in psychoneuroimmunology (PNI) at TAU’s Sagol School of Neuroscience and School of Psychological Sciences, and Prof. Oded Zamora of TAU’s Sackler Faculty of Medicine, who led the study.

“Our treatment reduced markers of metastasis in the tumor tissue and decreased the chances of cancer recurrence,” said Prof. Ben-Eliyahu.  “We deliberately sought the safest and cheapest drugs capable of lowering the body’s stress-inflammatory response to surgery in an effort to make high-quality care more accessible.”

For patients diagnosed with colon and rectal cancer, surgery to remove the tumor is the primary treatment. Unfortunately, with this type of cancer, the chance of postoperative metastasis among early-stage patients remains high at 35%. Prof. Ben-Eliyahu attributes this to both the physical and psychological strains of surgery:  “The stress during the waiting period for surgery, the stress and inflammatory reactions that the body produces during the surgery itself, the physical recovery period and finally the following anxiety of cancer recurring all have an adverse effect on the body’s ability to fight metastatic processes,” he explains.

Propranolol (Deralin), used to lower blood pressure and reduce anxiety, and etodolac (Etopan), used to prevent pain and inflammation, were administered to sixteen out of the 34 patients who participated in the trial. The remainder of the group was given a placebo. The treatment, beginning five days before surgery and lasting just 20 days, had minimal to no side effects on the patients. 

The hormones released in the body following surgery elicit stress-inflammatory responses, causing the release of prostaglandin and catecholamine hormones. These hormones suppress anti-metastatic immune activity, increasing the likelihood of developing metastases.

“In addition, these hormones directly help the cancer cells that remain in the body even after surgery. Due to exposure to these hormones, the cancerous tissue becomes more aggressive and metastatic,” Prof. Ben-Eliyahu explained. “The good news is that we know how to treat both stress and inflammation using off-the-shelf medications.”

After five years, only one-eighth (12.5%) of the patients who had received the drug combination developed metastases, whereas, in the control group, half of the patients developed metastases. 

The study was published under the title “Effect of perioperative COX-2 and beta-adrenergic inhibition on 5-year disease-free-survival in colorectal cancer: A pilot randomized controlled Colorectal Metastasis Prevention Trial (COMPIT)” in the European Journal of Surgical Oncology. At the same time, the researchers published an overview of the underlying theory and guiding principles used by the clinical trial in Nature Reviews Cancer under the title “Stress and cancer: mechanisms, significance, and future directions.”  

Although the findings are preliminary, Prof. Ben-Eliyahu and Prof. Zamora are optimistic as the results hold statistical significance, despite a limited scope. Currently, researchers are seeking funding to conduct a large-scale clinical trial to confirm their discovery and begin applying the treatment to patients as soon as possible.

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