Constipation-Relieving Drug May Improve Cancer Survival Rates

A medication for relieving opioid-induced constipation may slow tumor growth and increase survival rates in patients with advanced cancer, according to findings presented at Anesthesiology 2015.

Methylnaltrexone (MNTX; Relistor) relieves constipation caused by opioids, which are taken by nearly half of cancer patients for pain relief. The drug was developed by Jonathan Moss, MD, PhD, professor of anesthesia and critical care at the University of Chicago, and has been given to more than 800,000 patients since it was approved by the US Food and Drug Administration (FDA) in 2008.

There was early suspicion that MNTX might influence cancer’s progression. “I noticed that some of my patients lived much longer with the drug,” Dr. Moss told Clinical Pain Advisor. “I wondered if it was their nutrition or if it was something else.”

This led to 10 years in the lab examining the function of opiate receptors in tumor progression. Then during clinical trials to test the drug’s effect on bowel function, the researchers noticed fewer adverse events in the drug group, which led them to do an analysis of survival rates.

“This appears to be a receptor-mediated phenomenon and leads us to a new molecular target for cancer,” Dr. Moss said.

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The researchers examined data from two randomized clinical trials of patients with advanced cancer or other advanced diseases who did not respond to conventional laxatives. For one study, 229 patients including 151 with various types of advanced cancer including lung, prostate, breast, and pancreatic were either given MNTX or a placebo. For the other study, 134 patients including 78 with advanced cancers were either given MNTX or a placebo.

Among the 363 patients in both studies, 229 (63%) had cancer. The researchers assigned 117 patients to MNTX and 112 patients to placebo. Of the patients who received MNTX, 72 responded (62%) and 45 did not (38%). On average, the responders lived twice as long compared with non-responders or those who received the placebo (118 days vs 58 days).

Patients who had other serious diseases such as congestive heart failure, advanced chronic obstructive pulmonary diseases, or neurologic diseases did not have longer survival rates, even if they experienced relief from constipation.

“This makes it far less likely that improved bowel function is the only explanation for our finding of improved survival in cancer patients,” said Filip Janku, MD, assistant professor of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center in Houston in a press release. The researchers hypothesize that blocking the mu opioid receptor may lead to improved cancer outcomes.

Dr. Moss added that direct testing will be required to determine whether MNTX can be used to treat early-stage cancer or if it can help anesthesiologists improve care during surgery.

Disclosures: Dr. Moss receives royalties through the University of Chicago, is a developer of MNTX, and is a paid consultant for Salix Pharmaceuticals, which markets Relistor. This study was not sponsored by Salix Pharmaceuticals.

Reference

Moss J, Singleton PA, Johnson LK. Abstract #A4032. Effect of Methylnaltrexone on Overall Survival in Advanced Illness Patients With Cancer: A Post Hoc Analysis. Presented at: Anesthesiology 2015. Oct. 24-28, 2015; San Diego, California.