Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study

Integr Cancer Ther. 2023 Jan-Dec:22:15347354231178903. doi: 10.1177/15347354231178903.

Abstract

Background: Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy.

Objective: In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC).

Design: We conducted a retrospective analysis.

Methods: In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively.

Result: : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001).

Conclusion: Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.

Keywords: calcium channel blockers; cancer therapy; epidermal growth factor receptor tyrosine kinase inhibitors; non-small cell lung cancer; targeted therapy.

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms* / metabolism
  • Mutation
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use
  • Retrospective Studies

Substances

  • Calcium Channel Blockers
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • ErbB Receptors
  • Calcium Channels