We previously hypothesized that peripheral antagonism of opioid-mediated effects may attenuate disease progression in cancer patients. Therefore, we explored pooled data from two randomized, placebo-controlled registration trials in patients with advanced disease and examined those with cancer to identify whether peripheral mu opioid receptor antagonist methylnaltrexone, which is used for treatment of opioid induced constipation, could influence patients' survival. In this retrospective combined post-hoc analysis we demonstrated that in patients with advanced terminal cancers and opioid induced constipation, treatment with methylnaltrexone and even more so response to treatment are associated with prolonged survival compared to placebo (76 days vs. 56 days, P=0.033) or no response (118 days vs. 55 days, P<0.001). Of interest, this was not the case for patients with advanced terminal illness other than cancer, where survival was not affected. Our data are consistent with the emerging preclinical literature demonstrating an effect of mu opiates on tumor progression, and several recent studies relating opiate dose to recurrence in the perioperative lung cancer setting and in advanced prostate cancer. Nevertheless, 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. Prospective clinical studies to confirm the role of methylnaltrexone in patients with advanced cancers are merited to confirm clinical relevance of our findings.
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