Response to Methylnaltrexone Increased Overall Survival

Patients with advanced cancer treated with the peripheral μ-opioid receptor (MOR) antagonist methylnaltrexone (MNTX) had longer overall survival than patients treated with placebo, according to the results of a study published in Annals of Oncology.

“While our findings are in patients with advanced malignancies, the hypothesis that μ-opioid antagonism may have a potential therapeutic value also extends to earlier tumors and to the perioperative period,” wrote Filip Janku, MD, PhD, of the University of Texas MD Anderson Cancer Center, and colleagues. “Our findings should be interpreted as preliminary, hypothesis-generating, and insufficient to mandate a change in clinical practice, where pain control remains an important issue.”

MNTX is currently approved in the United States for the treatment of opioid-induced constipation (OIC). MNTX binds to the MOR in periphery, thereby blocking opioid drugs from binding to that same receptor. In this study, Janku and colleagues examined whether MNTX given at regular doses affected survival of patients with advanced cancer.

They pooled data from two studies of patients with OIC despite laxatives. Patients were randomly assigned to MNTX (n = 117) or placebo (n = 112) during the double-blind phase of the study. Later, patients were permitted to cross over to MNTX treatment. The most common cancer types were lung (25%), prostate (13%), breast (10%), and pancreatic cancers (7%).

Median overall survival was longer in patients treated with MNTX compared with placebo (76 days vs 56 days; P = .033). Sixty-two percent of patients assigned MNTX had response to treatment within 4 hours after the first administration compared with only 4% of patients assigned placebo (P < .001). The 72 patients who responded to MNTX had a significantly longer median overall survival compared with patients assigned MNTX without response (118 days vs 58 days; P = .001).

“While our observations of longer overall survival in patients with MNTX could be partially explained by direct effects improving gut function, or an indirect effect such as immunosuppression, we favor a direct effect of the drug on tumors as an explanation of our observations,” the researchers wrote.

Including patients who crossed over, the 77 patients who responded to MNTX had a longer overall survival than the 152 patients who did not (118 days vs 55 days; P < .001).

The researchers found two independent prognostic factors for increased overall survival: response to therapy (hazard ratio [HR], 0.47 [95% CI, 0.29–0.76]; P = .002) and albumin levels of 3.5 or greater (HR, 0.46 [95% CI, 0.30–0.69]; P < .001).

“It still remains unclear whether MOR can mediate disease progression irrespective of tumor type or whether this mechanism is more important for certain specific cancers. Our findings suggest that lung and pancreatic cancer may be good targets for further investigations,” noted the researchers.