Phase II trial of subcutaneous methylnaltrexone in the treatment of severe opioid-induced constipation (OIC) in cancer patients: an exploratory study.

Abstract

Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that has been shown to relieve severe opioid-induced constipation (OIC) in patients with advanced disease receiving palliative care. Its efficacy remains unknown in cancer patients who are not terminally ill. The primary aim of this study was to evaluate the efficacy of methylnaltrexone over 48h in cancer patients who were not terminally ill. In this single-dose phase II trial, cancer patients with a prognosis of ≥3months and OIC with <3 laxations during the preceding week were eligible. The primary endpoint was a rescue-free laxation ≤4h after a single dose of methylnaltrexone. Friedman's two-way analysis of variance was conducted for the number of laxations, pain and withdrawal scales, and laxation- and constipation-related symptoms. Univariate/bivariate Cox proportional hazard models for laxation times were employed. Twelve patients received methylnaltrexone. Eleven patients had an ECOG performance status of 1 or 2. Four (33.3%) and 5 (41.7%) patients had rescue-free laxation within 4 and 24h, respectively, and 10 (83.3%) had laxation within 48h (p=0.006). Difficulty passing a stool improved significantly over 48h (p=0.029). The bivariate Cox models revealed that a shorter time to laxation was associated with a higher baseline morphine equivalent daily dose (hazard ratio, 1.02 per 1mg; p=0.018) and a smaller number of laxations in the preceding week (hazard ratio, 0.13 per one laxation; p=0.035). Patients tolerated methylnaltrexone well without opioid withdrawal. Methylnaltrexone may relieve severe OIC in cancer patients who are not terminally ill. A larger prospective study is justified in this population. (NCT01004393, https://clinicaltrials.gov/show/NCT01004393 ).