• Masanori Mori, Yongli Ji, Santosh Kumar, Takamaru Ashikaga, and Steven Ades.
• Palliative Care Team, Seirei Mikatahara General Hospital, 3453, Mikatahara-cho, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan. masanori.mori@sis.seirei.or.jp.
• Int. J. Clin. Oncol. 2017 Apr 1; 22 (2): 397-404.

BackgroundMethylnaltrexone 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 48 h in cancer patients who were not terminally ill.MethodsIn this single-dose phase II trial, cancer patients with a prognosis of ≥3 months and OIC with <3 laxations during the preceding week were eligible. The primary endpoint was a rescue-free laxation ≤4 h 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.ResultsTwelve 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 24 h, respectively, and 10 (83.3 %) had laxation within 48 h (p = 0.006). Difficulty passing a stool improved significantly over 48 h (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 1 mg; 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.ConclusionsMethylnaltrexone 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 ).

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