Methylnaltrexone treatment of opioid-induced constipation in cancer patients

Abstract

9081 Background: Constipation is a common and distressing side effect of opioid treatment particularly in patients with cancer. Two phase 3 trials (Studies 301 and 302) reported that subcutaneous (SC) methylnaltrexone was well tolerated and effective in inducing laxation in patients with advanced illness with opioid-induced constipation (OIC) while maintaining central analgesia. Aims: To evaluate improvement in constipation in cancer patients treated with methylnaltrexone in the above studies. Methods: In Study 301, 124 cancer patients received a single dose of methylnaltrexone (SC 0.15mg/kg, 0.30mg/kg) or placebo. In Study 302, 78 cancer patients received either 0.15mg/kg SC QOD methylnaltrexone for 2 weeks (total of 7 doses) or placebo. Patients had a life expectancy of 1–6 months, no laxation within 48 hours, and were maintained on stable opioids and baseline laxatives. The primary efficacy endpoints were laxation within 4 hours after a single or first dose of study drug and laxation within 4 hours for at least 2 of the first 4 doses (Study 302). The secondary endpoints were laxation within 24 hours, pain scores, and opioid withdrawal symptoms. Results: A majority of the methylnaltrexone-treated cancer patients had a laxation within the first 4 hours of study drug administration ( Table ). There were no clinically significant changes in pain scores or opioid withdrawal symptoms. Conclusions: Our results demonstrate that in cancer patients with advanced illness and OIC, methylnaltrexone significantly improved constipation, without loss of pain control or opioid withdrawal. [Table: see text] No significant financial relationships to disclose.