Many cancer-related deaths are the result of the reoccurrence of cancer after surgery. This is referred to as post-surgical metastasis. In metastasis, cells of primary tumors travel to other parts of the body, where they often proliferate into inoperable, ultimately fatal growths. Most doctors think that these metastatic cancers were spread before the surgery. But that may not be the case.
In the last 20 years, animal studies have shown that there’s something about the psychological and physiological stress and inflammation that comes with surgery. And this can cause cancer cells to metastasize during the surgery. Now, researchers at Tel Aviv University, in collaboration with the University of California at Los Angeles and three Israeli hospitals, say they have found a specific drug regimen for these cancer patients. When they give this drug to patients before and after surgery, it “significantly reduces the risk of post-surgical cancer recurrence.”
Previous studies have shown that there’s a reason surgery can cause a tumor to metastasize. It’s because it stimulates an excessive release of natural hormones called catecholamines and prostaglandins right before and during the surgery. So, the researchers in this study decided to try giving patients two drugs that decreased the release of these hormones. The medications are a combination of a beta blocker called propranolol, which is used to treat blood pressure, and an anti-inflammatory COX-2 inhibitor drug called etodolac (trade name Lodine). Doctors typically use this drug to treat the symptoms of arthritis. The two medications are similar in price to aspirin, and are easily administered to patients without contraindications.
For the study, the researchers gave 38 breast cancer patients etodolac 400 mg, twice daily for five days before surgery, the day of surgery, and five days after surgery. They gave extended release propranolol as follows: 20 mg twice a day for the five days preceding surgery; 80 mg on the morning of surgery and on the evening and morning following surgery; and 20 mg twice a day for five days after surgery.
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After they removed the tumors, the researchers checked the molecular traits of the tumor and discovered an amazing finding. The drug treatment made the tumors less metastatic. According to lead author Professor Ben-Eliyahu, “We found that the drugs were very efficient in reducing biomarkers of metastatic processes.” He also added, “For example, we found that the drug treatment reverses EMT – the process that tumor cells go through to slip out of the primary tumor and enter another organ. It’s a crucially important step in the metastatic process.” And that’s not all.
They also discovered that the drugs improved the function of the cells called natural killer cells that the immune system uses to kill cancer cells before they spread. The authors did not mince words, “Perioperative [before and during surgery] inhibition of COX-2 and ß-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer.” And it doesn’t appear that this effect happens only to breast cancer cells.
The same research team conducted a similar, as-yet-unpublished study on colorectal cancer patients, and found similar results. But here’s a sad commentary on today’s medicine. Professor Ben-Eliyahu said that although larger scale experiments are needed to further study the drugs, it isn’t likely to happen. Why? “Because the drugs used are generic medications and not protected by patents, and big pharma firms may not be interested in pursuing such research.”
If you are going to have surgery to remove a cancer, it makes good sense to discuss with your doctor about taking extended release propranolol along with etodolac for five days before surgery, on the day of surgery, and for five days after surgery. Propranolol can lower blood pressure and etolodac can increase bleeding tendency. But as long as your doctor knows about it, they can easily counter these effects.
Yours for better health,
Frank Shallenberger, MD
Shaashua L, Shabat-Simon M, et al.
Perioperative COX-2 and ß-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin Cancer Res. 2017 Aug 15;23(16):4651-4661.
“Simple drug regimen could help prevent cancer recurrence, Israeli study says,” By Shoshanna Solomon, August 8, 2017, 1:16 pm 4