A research group from Tel Aviv University (TAU) successfully reduced metastatic spread following tumor removal surgery in colorectal cancer patients. Using a short medication treatment around the time of the surgery, the researchers were able to reduce body stress responses and physiological inflammation during this critical period, preventing the development of metastases in the years following the surgery.
The study, which was published in the journal Cancer on June 13, was led by Prof. Shamgar Ben-Eliyahu from TAU's School of Psychological Sciences and Sagol School of Neuroscience and Prof. Oded Zmora from Shamir (Assaf Harofeh) Medical Center.
During the three-year-long study, researchers monitored 34 patients who received treatment surrounding a colorectal tumor removal surgery. During the pre- and post-surgical period, patients were administered two safe and known drugs: Propranolol (Deralin), an anti-anxiety and blood pressure reducing drug; and Etodolac (Etopan), an anti-inflammatory analgesic. The drugs were administered to the patients for 20 days -- from five days before surgery to two weeks after. Half of the patients received a placebo treatment as a control group.
The results were highly promising. While only 12.5% (2 out of 16) of patients receiving the drug treatment exhibited metastatic disease, the rate of metastases development was found to be 33% (6 out of 18 patients) in the control group, the known rate of metastasis for colorectal cancer patients. Prof. Ben-Eliyahu says that he is highly satisfied with these data, but also states that "despite the impressive results, this treatment must be examined again, in a much larger number of patients, in order to test whether it is, in fact, life-saving."
According to Prof. Ben-Eliyahu, the study of molecular markers in the cancerous tissue excised from the patients showed that the treatment with the medications led to a reduction in the metastatic potential of the tumor and potentially the residual cancer cells. In addition, the drugs triggered some beneficial alterations in the number and type of infiltrating tumor leukocytes (patients' white blood cells), markers that iindicate a reduced chance of disease recurrence.
When the body is in a state of stress, whether physiological (from surgery) or psychological, this causes a release of high amounts of two types of hormones, prostaglandins and catecholamines. These hormones suppress the activity of the immune cells, indirectly promoting the development of cancer metastases. In addition, these hormones also directly promote the acquisition of metastatic traits in cancer tissue. Our study shows that inexpensive, accessible medication treatment could be used in order to reduce body stress responses and inflammation associated with surgery, which affects the tumor, significantly reducing the risk of metastases that might be detected months or years after surgery."
Prof. Shamgar Ben-Eliyahu from TAU's School of Psychological Sciences and Sagol School of Neuroscience
Following the success of the initial research, Prof. Ben-Eliyahu and Prof. Zmora are encouraging Israeli colorectal and pancreatic cancer patients to apply for participation in a large-scale clinical study now starting across Israel.
Haldar, R., et al. (2020) Perioperative COX2 and β‐adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial. Cancer. doi.org/10.1002/cncr.32950.