Addiction, nausea, constipation and respiratory depression aren’t the only health risks associated with opioid use. You can add cancer to the list. Two new studies have found the painkilling drugs may stimulate the growth and spread of tumors in cancer patients.
Laboratory research at the University of Chicago Medicine and a genetic study at the University of North Carolina Medical Center both argue that an opioid receptor in the body plays an important role in tumor progression. The studies and a commentary about them are being published in Anesthesiology, the journal of the American Society of Anesthesiologists.
“Epidemiologic findings suggest that the type of anesthesia we do for cancer surgery influences recurrence rate, and laboratory studies demonstrate that opioids influence tumor progression and metastasis,” said Jonathan Moss, MD, PhD, professor of anesthesiology and critical care at the University of Chicago Medicine and co-author of the commentary. “These studies have caused anesthesiologists to re-evaluate how best to do anesthesia and pain control for cancer patients.”
Opioid-based painkillers, such as morphine, have been used for treatment of postoperative and chronic cancer pain for 200 years.
The University of Chicago study found that cells from various types of human lung cancers have five to 10 times as many opioid receptors as non-cancerous lung cells. When transplanted into mice, the cancer cells with additional copies of the opioid receptor grew more than twice as fast as tumor cells that lacked the extra receptors. More troubling, they were 20 times more likely to metastasize and spread to other parts of the body.
Researchers also found that drugs that block the opioid receptors, such as naloxone or methylnaltrexone, reduced the growth and spread of tumors. Dr. Moss and his colleagues at the University of Chicago were involved in clinical trials of methylnaltrexone, a drug approved by the Food and Drug Administration in 2008. The drug, sold under the brand name Relistor, was designed to block the peripheral side effects of opioids, such as nausea and constipation, without disrupting pain relief. During one clinical study, Moss noted that cancer patients receiving methylnaltrexone lived longer than expected.
“These were patients with advanced cancer and a life expectancy of one to two months,” Moss recalled, “yet several lived for another five or six months. It made us wonder whether this was just a consequence of better GI function, or could there possibly be an effect on the tumors?”
They began a series of studies looking at the many side effects of opioids and the potential benefits of blocking them. They found that opioids enhanced tumor growth, angiogenesis, vascular permeability and metastasis. Drugs that blocked the opioid receptor reduced cancer growth and helped prevent invasion and metastasis. While the research suggests that methylnaltrexone and other drugs that suppress opioid receptors could have value in cancer treatments, Moss and his colleagues caution that “there are no clinical trials in humans demonstrating a direct effect.”
Methylnaltrexone is a derivative of naltrexone, which is currently being studied for treatment of fibromyaligia.
The other paper in the journal, the study at the University of North Carolina, used human data to bolster the opioid-cancer link.
Researchers looked at survival rates from an earlier study of more than 2,000 breast cancer patients. Women being treated for invasive breast cancer who had a genetic mutation that made them less sensitive to opioids were much more likely to be alive 10 years after cancer treatment. Women with one copy of the protective mutation were nearly twice as likely to have survived and those with two copies were four times as likely.