Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer.

Purpose: Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.

Methods: A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan-Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.

Results: 4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4-7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8-7.8) vs. 6.7 months (95% CI 6.4-7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7-11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5-8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9-22%) and 14.8% (95% CI 11.1-19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2-4.4%).

Conclusion: Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.