New drug promises pain relief for many terminal cancer patients

A drug developed at the University to help a researcher’s dying friend reverses one of the most troubling problems caused by opium-based pain relievers, according to a study by researchers at the University Medical Center.

The research and the drug’s effectiveness were reported in the Jan. 19 issue of JAMA, the journal of the American Medical Association.

Each year, more than 250,000 terminal cancer patients take opioids, such as morphine, for pain relief. About half of those patients experience constipation so severe that many choose to forego the pain relief in order to avoid the constipation.

In a new double-blind, placebo-controlled study, methylnaltrexone promptly reversed opioid-induced constipation without side effects. In more than 90 percent of patients, relief came within one minute of the first infusion.

“By preventing this debilitating but little-discussed problem, methylnaltrexone could substantially enhance the quality of the last months of life for terminal cancer patients and others who depend on opioid pain relievers,“ said the study’s first author Chun-Su Yuan, Assistant Professor in Anesthesia & Critical Care.

The late University pharmacologist Leon Goldberg, who wanted to help a dying friend suffering from morphine-induced constipation, invented methylnaltrexone in 1979.

Goldberg started with naltrexone, an established drug that completely blocks the effects of morphine. He altered the drug slightly by attaching a methyl group that changed the charge of the molecule so it could no longer cross the protective barrier that surrounds the brain.Consequently, it did not interfere with morphine’s effects on pain, which is centered in the brain, but it did block morphine’s effects on gut motility, which are mediated by receptors in the peripheral gastrointestinal tract.

The initial success of the drug in this compassionate-use setting drew the attention of Goldberg’s colleagues, who continued to develop the compound following Goldberg’s death.

In the recent study, rather than risk interrupting pain relief for patients with terminal cancer, the researchers focused on 22 volunteers who were enrolled in a methadone-maintenance program for opioid addiction. All 22 volunteers suffered from opioid-induced constipation, which affects about 60 percent of long-term metha-done users.

The next step, said the researchers, is to find a U.S. pharmaceutical company to support a phase-III clinical trial involving patients with advanced cancer.

One trial, using an oral preparation, is already underway with cancer patients receiving palliative care at St. Christopher’s Hospice, near London.

The research was supported by grants from the American Cancer Society, the International Anesthesia Research Society, the Clinical Practice Enhancement and Anesthesia Research Foundation and the U.S. Public Health Service.

More information on the drug is available at http://mntx.uchicago.edu.