The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

Darren M. Brenner*, Neal E. Slatkin, Nancy Stambler, Robert J. Israel, Paul H. Coluzzi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods: This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results: Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion: Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

Original languageEnglish (US)
JournalSupportive Care in Cancer
DOIs
StateAccepted/In press - 2021

Keywords

  • Analgesics
  • Constipation
  • Methylnaltrexone
  • Narcotic antagonists
  • Opioid
  • Pain management

ASJC Scopus subject areas

  • Oncology

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