Background: Basic research has suggested that adrenergic activation can promote PDAC growth. Here we investigate the impact of Beta- blockers (BB) in resected PDAC patients. Method: Patients from two European pancreatic centers after resection of PDAC between 2002 and 2012 (n1⁄4595) were studied. 159 patients received BB. Seventeen patients with non-selective-BB (NSBB) were compared to 85 patients receiving no-BB (NBB) using a matched-pair analysis (1:5 scenario). 142 patients with beta1-selective agents (SB1B) were also studied. Univariate and multivariate survival analysis (Cox) was performed. Microtumors from PDAC were generated and treated with SB1B, beta2-selective blockers (SB2B; ICI118,551) and NSBB (propranolol) in addition to GEM. Results: The median age was 70 years (22-88 years). For patients receiving any beta-blocker, the median OS was 25 vs. 21 mo for NBB (p1⁄40.0084). The median OS of patients receiving UBB was 40 vs. 23 mo for NBB (p1⁄40.0007) and 21 mo for patients with SB1B (p1⁄40.0396). Hyper- tension (HPT) was associated with decreased OS across all groups. Even among patients with HPT, a longer median OS was observed among UBB compared with NBB (40 vs 19 mo; p1⁄40.041). Microtumors when treated using NSBB or SB2B in addition to GEM showed a significantly lower re- sidual metabolic activity (p1⁄40.032). Conclusion: For the first time a matched pair analysis comparing administration of NSBB to SB1B and NBB in PDAC patients is presented. UBB almost doubled OS in PDAC in an adjuvant setting, while SB1B did not show a difference. This data implicates that targeted therapy of the adrenergic beta2-pathway might be a promising therapeutic strategy in the treatment PDAC.

Clinical impact of nonselective beta-blockers on survival in patients with pancreatic cancer- revival of well known drugs?

Marina Macchini
Writing – Original Draft Preparation
;
Riccardo Casadei
Membro del Collaboration Group
;
Mariacristina di Marco
Membro del Collaboration Group
;
2017

Abstract

Background: Basic research has suggested that adrenergic activation can promote PDAC growth. Here we investigate the impact of Beta- blockers (BB) in resected PDAC patients. Method: Patients from two European pancreatic centers after resection of PDAC between 2002 and 2012 (n1⁄4595) were studied. 159 patients received BB. Seventeen patients with non-selective-BB (NSBB) were compared to 85 patients receiving no-BB (NBB) using a matched-pair analysis (1:5 scenario). 142 patients with beta1-selective agents (SB1B) were also studied. Univariate and multivariate survival analysis (Cox) was performed. Microtumors from PDAC were generated and treated with SB1B, beta2-selective blockers (SB2B; ICI118,551) and NSBB (propranolol) in addition to GEM. Results: The median age was 70 years (22-88 years). For patients receiving any beta-blocker, the median OS was 25 vs. 21 mo for NBB (p1⁄40.0084). The median OS of patients receiving UBB was 40 vs. 23 mo for NBB (p1⁄40.0007) and 21 mo for patients with SB1B (p1⁄40.0396). Hyper- tension (HPT) was associated with decreased OS across all groups. Even among patients with HPT, a longer median OS was observed among UBB compared with NBB (40 vs 19 mo; p1⁄40.041). Microtumors when treated using NSBB or SB2B in addition to GEM showed a significantly lower re- sidual metabolic activity (p1⁄40.032). Conclusion: For the first time a matched pair analysis comparing administration of NSBB to SB1B and NBB in PDAC patients is presented. UBB almost doubled OS in PDAC in an adjuvant setting, while SB1B did not show a difference. This data implicates that targeted therapy of the adrenergic beta2-pathway might be a promising therapeutic strategy in the treatment PDAC.
2017
Bernhard W. Renz, Barbara Mayer, Marina Macchini, Timothy C. Wang, Riccardo Casadei, Mariacristina di Marco, Axel Kleespies, Jens Werner
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/628811
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