ArticleThe oncologist2025
A phase 0, window of opportunity study of parasympathetic stimulation with bethanechol in localized pancreatic adenocarcinoma prior to surgery.
Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03572283 (Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery), which is not on this map. Cited by 2 papers.
What it found
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The trial behind it
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Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery
Who cites it
2 citing papers in PubMed.
- Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.Journal of neuroinflammation · 2026Review
- Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundThe parasympathetic branch of the autonomic nervous system has shown tumor-suppressive effects in preclinical models of pancreatic adenocarcinoma (PDAC) by inhibiting cancer stem cells and suppressing inflammatory cytokine production. Based on these findings, we hypothesized that bethanechol, an FDA-approved parasympathomimetic agent targeting muscarinic receptors, could enhance treatment efficacy in PDAC.
methodsWe conducted a phase 0/window of opportunity study evaluating short-term parasympathetic activation with fixed dose bethanechol (100 mg twice daily) in subjects with resectable or borderline resectable PDAC prior to surgery. The primary endpoint was a change in cell proliferation by Ki-67 expression compared to stage-matched controls. Secondary endpoints included tissue expression of stem cell markers (CD44), infiltrating immune cells (CD8a, Granzyme B, and CD68), and changes in circulating inflammatory cytokine concentrations.
resultsSeventeen patients were enrolled with 13 eligible for analysis of endpoints. Median age was 74 (59-86), 6 female (46%), all ECOG 0-1, and median duration of treatment was 8 days (7-13). R0 resections were achieved in 9 patients (69%). There was no difference in Ki67 and CD44 tissue biomarkers between bethanechol-treated and control samples. Decreased numbers of Granzyme B-expressing cells were seen in bethanechol-treated tissues. Bethanechol treatment was associated with the suppression of circulating IL-18. The most common treatment-related adverse events (TRAE) were hot flashes (30.7%), urinary frequency (15.4%), increased salivation (15.4%), hyperhidrosis (7.7%), and nausea (7.7%). There were no Grade 3 or higher adverse effects. No surgical complications were attributed to bethanechol treatment.
conclusionBethanechol 100 mg twice daily is well tolerated in patients with PDAC in this small phase 0/window of opportunity study (NCT03572283). Bethanechol treatment was associated with decreased Granzyme B positive cells and decreased circulating IL-18 consistent with an anti-inflammatory role for parasympathetic muscarinic signaling in PDAC.
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