A constipation drug extends survival in advanced cancer patients
A constipation drug extends survival in advanced cancer patients
27 Oct 2015Patients with advanced cancers who took a drug designed to relieve constipation caused by pain killers lived longer and had fewer reports of tumor progression than cancer patients who did not receive the drug. This is the first study in humans to associate opioid blockade with improved survival.
The finding suggests that the drug, methylnaltrexone, approved for use by the United States FDA in 2008 to treat opioid-induced constipation, could play a role in cancer therapy.
"Early on, we began to suspect that methylnaltrexone might inhibit cancer growth" said Jonathan Moss, MD, PhD, lead author of the study and professor of anesthesia and critical care at the University of Chicago. "After more than a decade in the lab trying to assess how methylnaltrexone affects cancer, we have the first evidence that it can decrease tumor growth and extend survival in patients who respond to the drug."
Increased survival rates in patients responding to the drug
The study, a retrospective survival analysis, included 229 patients who participated in two randomized, controlled clinical trials focused on relief of constipation for patients receiving palliative care for various types of late-stage cancer and other terminal diseases. None of the patients enrolled responded to conventional laxatives.
In these two trials, 117 cancer patients received methylnaltrexone (marketed as Relistor®) for opioid-induced constipation, while 112 were given a placebo. 57% of the patients who received methylnaltrexone experienced relief from constipation; 43% did not.
According to the researchers, the analysis of the results revealed that:
- Those who received and responded to methylnaltrexone lived, on average, twice as long (118 days versus 58 days) as those who did not respond or were given the placebo.
- Patients who responded to methylnaltrexone also had significantly fewer reports of tumor progression (7.6%) compared to those who did not respond (22%) or who took the placebo (25.4%), based on physician reports of adverse events.
No additional survival in patients with advanced illnesses other than cancer
The researchers also analyzed the effects of methylnaltrexone on another 135 patients from the same trials who had advanced illnesses other than cancer, such as congestive heart failure, advanced chronic obstructive pulmonary disease or neurologic diseases. Methylnaltrexone relieved constipation for more than half of the patients, but brought no additional survival, even for those who responded to the drug's digestive effects.
"This makes it far less likely that improved bowel function is the only explanation for our finding of improved survival in cancer patients," said study co-author Filip Janku, MD, PhD, assistant professor of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center in Houston.
"We are not precisely sure why methylnaltrexone was associated with fewer reports of tumor progression and longer survival in our patients," Janku said. "Proving what causes this response is very difficult. But it could be that methylnaltrexone influences several side effects of opioids unrelated to pain relief. The findings are consistent with what we saw in the lab."
Source: Science Daily