Opioid Blockade for Constipation May Play Role in Cancer Therapy

A drug commonly given to cancer patients to relieve opioid-induced constipation is capable of slowing tumor growth and may play a role in developing new drug therapies, according to an analysis presented at last week’s 2015 American Society of Anesthesiologists in San Diego.

Investigators conducted a retrospective survival analysis of 229 patients with serious illnesses who were given either methylnaltrexone (117) or placebo (112) for opioid-induced constipation. Fifty-seven percent of those who received methylnaltrexone experienced relief from symptoms, and that group also lived twice as long as patients who did not respond to the drug or were given placebo (118 vs 58 days).

Taking methylnaltrexone was also associated with fewer reports of tumor progression: 7.6% compared with 22% among those who did not respond to therapy and 25% in the control group. The analysis looked at two trials in which patients were receiving palliative care for cancer and other terminal illnesses and had not responded to conventional laxatives.

“Early on, we began to suspect that methylnaltrexone might inhibit cancer growth,” said Jonathan Moss, MD, PhD, the study’s lead author 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.”

Investigators also analyzed the effects of methylnaltrexone on 135 patients involved in the same trials who had diseases other than cancer, including congestive heart failure and advanced chronic obstructive pulmonary disease. Although methylnaltrexone relieved constipation in more than half of these patients, it was not associated with longer survival, suggesting that the drug may play a role in inhibiting tumor growth.

“We are not precisely sure why methylnaltrexone was associated with fewer reports of tumor progression and longer survival in our 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. “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."

Methylnaltrexone is an opioid receptor antagonist approved by the US Food and Drug Administration that is given to cancer patients to counteract opioid-induced constipation without interfering with analgesia. In previous studies in animal models, methylnaltrexone reduced growth of tumors and improved survival in several types of cancer. It also appears to affect cancer cell growth in the absence of opioids, suggesting that the opioid receptor pathway may be an important therapeutic target to explore.

Future research should focus on whether the findings can be extended to treating earlier-stage cancers, the researchers said. Methylnaltrexone may also potentially play a role in improving care during cancer surgeries.

“This study raises novel questions about the role of the opiate receptor in cancer progression,” said Ralph Weichselbaum, MD, chairman of radiation oncology and co-director of the Ludwig Center for Metastasis Research at the University of Chicago. “Could the opiate receptor become a therapeutic target? What are the significant side effects of opiates in cancer care? This is an important, hypothesis-generating result.”