Impact of Concurrent Medication Use on Pancreatic Cancer Survival—SEER-Medicare Analysis

Beg, Muhammad Shaalan; Gupta, Arjun; Sher, David J.; Ali, Sadia; Gao, Ang; Stewart, Tyler F.; Ahn, Chul; Berry, Jarett D.; Mortensen, Eric M.

doi:10.1097/coc.0000000000000359

Cited by 35 publications

(31 citation statements)

References 43 publications

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“…No clear rate differences were observed by β-blocker receptor selectivity owing to very few patients on NSBB. A SEER-Medicare analysis also showed improved survival in patients with PDAC on β-blocker therapy (Beg et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

“…In addition, cancer mortality is significantly increased by high levels of psychological stress (Batty et al, 2017). On the other hand, it is suggested that β-blocker treatment of patients suffering from colorectal cancer (Jansen et al, 2014), breast cancer (Barron et al, 2011), ovarian cancer (Watkins et al, 2015), melanoma (Lemeshow et al, 2011), and PDAC (Beg et al, 2017; Udumyan et al, 2017), may lead to improved survival.…”

Section: Introductionmentioning

confidence: 99%

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β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

et al. 2018

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Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras;LSL-Trp53;Pdx1-Cre (KPC) mice. Therapy with a Trk inhibitor together with gemcitabine also increased survival of KPC mice. Analysis of PDAC patient cohorts revealed a correlation between brain-derived neurotrophic factor (BDNF) expression, nerve density, and increased survival of patients on nonselective β-blockers. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

et al. 2018

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“…Moreover, the pooling analysis by Zhang et al indicated that metformin may improve the survival for cancer patients with concurrent diabetes, particularly for breast, colorectal, ovarian, and endometrial cancer, but they failed to show such survival benefit in pancreatic cancer with only 3 studies included (HR=0.80, 95% CI= 0.62-1.03) [14]. Additionally, a recent meta-analysis combining 27 studies comprising 24178 participants was conducted to qualify the adjuvant effect of metformin in cancers, suggesting a better survival, particularly in colorectal and prostate cancer, however without special attention to pancreatic cancer Reni,2016 [26] Italy ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Lee,2016 [27] Korea ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 Ambe,2016 [21] USA ▲ ▲ ▲ ▲ ▲ ▲ 6 Cheon,2014 [28] Korea ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Hwang,2013 [29] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 9 Amin,2016 [30] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Kordes,2015 [31] Netherlands ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 9 Chaiteerakij,2016 [32] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Sadeghi,2012 [33] USA ▲ ▲ ▲ ▲ ▲ ▲ 6 Cerullo,2016 [34] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 Kozak,2016 [35] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 Toomey,2015 [36] USA ▲ ▲ ▲ ▲ ▲ 5 Choi,2015 [37] Korea ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Beg,2017 [38] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 Jang,2017 [39] Korea ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ 8 Frouws,2017 [40] Netherlands ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 E,2017 [41] USA ▲ ▲ ▲ ▲ ▲ ▲ ▲ 7 [46] and by E et al (6 studies with 12,057 participants) have represented similar findings with demonstrating a survival benefit of metformin therapy for pancreatic cancer patients [47]. Furthermore, the subgroup analyses based on ethnicity in the current study revealed a more favorable prognosis for metformin therapy in Asian population (HR=0.74, P=0.01) but not evident in Caucasian population (HR= 0.92, P=0.10) which was in line with the findings by Zhou et al, indicating that ethnicity variation may contribute to the metformin action, however, the underlying mechanism for the discrepancy remains undefined.…”

Section: Discussionmentioning

confidence: 99%

Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis

Wan

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Previous studies on the effect of metformin therapy on survival of pancreatic cancer patients obtained inconsistent findings. To reevaluate the prognostic value of metformin adjuvant treatment, a meta-analysis was carried out. Methods: Relevant articles addressing the association between metformin use and pancreatic cancer survival were electronically searched to identify eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Results: Totally, seventeen studies involving 36791 participants were included. Overall, metformin use was found to be significantly associated with a favorable OS (HR=0.88, 95% CI=0.80-0.97). Subgroup analyses by ethnicity showed a significantly reduced risk of death for metformin users compared with non-users in Asians (HR=0.74, 95% CI=0.58-0.94) but nonsignificant in Caucasians. When stratified by clinical stage, a remarkable reduction of mortality risk in patients at stage I-II treated with metformin (HR=0.76, 95% CI=0.68-0.86) was found as well as the group at stage I-IV (HR=0.88, 95% CI=0.79-0.99), but not in patients at stage III-IV. In the stratification analyses based on treatment strategy, metformin therapy was found to be associated with a better clinical outcome in patients receiving surgery or comprehensive therapy (HR=0.73, 95% CI=0.62-0.87; HR=0.88, 95% CI=0.79-0.97) but not chemotherapy. However, the overall analysis failed to show a significant association between metformin use and DFS (HR=1.54, 95% CI=0.94 -2.50) with only 2 studies enrolled. Conclusion: The current study has evidenced a significant association of metformin adjuvant treatment with the survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment. Further investigation is needed.

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“…However encouraging the results from experimental studies may be, the role of beta-blockers in cancer patients remains unclear and the results from mostly retrospective observational studies are equivocal. There are studies suggesting the use of beta-blockers may be able to prolong survival of cancer patients [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. On the other hand, there are also studies that do not support such a hypothesis [50][51][52][53][54][55][56][57][58][59][60].…”

Section: Discussionmentioning

confidence: 99%

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

Fiala

Ostasov

Šorejs

et al. 2019

Cancers

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Background: Beta-adrenergic signalling plays an important role in several cancer-related processes, including angiogenesis. The impact of beta-blocker use on prognosis of cancer patients treated with antiangiogenic agents is unclear. The aim of this study was to evaluate the association between the incidental use of beta-blockers and the outcomes of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based therapy. Methods: Clinical data from 514 mCRC patients treated with bevacizumab between 2005 and 2019 were analysed retrospectively. The association of progression-free survival (PFS) and overall survival (OS) with the incidental use of beta-blockers and other common antihypertensive drugs was assessed. Results: The median PFS and OS for patients using beta-blockers was 11.40 (95% confidence interval (CI) 10.10–13.61) months and 26.8 (95% CI 22.2–32.2) months compared with 8.30 (95% CI 7.80–9.57) and 21.0 (95% CI 17.8–23.8) months for patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate analysis, the use of beta-blockers was a significant factor predicting both PFS (hazard ratio (HR) = 0.763 (95% CI 0.606–0.960), p = 0.021) and OS (HR = 0.730 (95% CI 0.560–0.951), p = 0.020). Conclusions: The results of the present retrospective study suggest that there is a significant association between the use of beta-blockers and favourable outcomes of mCRC patients treated with bevacizumab-based therapy.

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Impact of Concurrent Medication Use on Pancreatic Cancer Survival—SEER-Medicare Analysis

Abstract: In this study, use of β-blockers, heparin, insulin, and warfarin were associated with improved survival in patients with pancreatic cancer. Additional studies are needed to validate these findings in the clinical setting.

Cited by 35 publications

References 43 publications

β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer

Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis

Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients

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