Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy

J Cancer Res Clin Oncol. 2009 Oct;135(10):1429-35. doi: 10.1007/s00432-009-0587-3. Epub 2009 Apr 28.

Abstract

Purpose: The renin-angiotensin system plays a crucial role in maintaining vascular homeostasis. Stimulation of angiotensin II type 1 receptors (AT1R) acts proangiogenically by increasing levels of vascular endothelial growth factor (VEGF). Consequently, cell culture experiments and animal studies have shown antiproliferative effects of AT1R blockers (ARB) and angiotensin I converting enzyme inhibitors (ACEI) in several malignancies. Until now, very limited clinical data for this antiangiogenic effect exists for combinations with antineoplastic chemotherapy.

Methods: A total of 287 patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy were retrospectively analysed regarding long-term medication with ACEI and ARB as well as histological type, stage, performance status, gender, age, dose-intensity of chemotherapy and survival.

Results: Patients receiving either ACEI or ARB had a 3.1 months longer median survival than non-recipients (11.7 vs. 8.6 months, HR 0.56, P = 0.03). This survival advantage could not be attributed to other established risk-factors or dose intensity of chemotherapy.

Conclusions: Addition of ACEI or ARB to platinum-based first-line chemotherapy may contribute to prolonged survival in patients with advanced lung cancer.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Carcinoma, Adenosquamous / drug therapy
  • Carcinoma, Adenosquamous / mortality
  • Carcinoma, Adenosquamous / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Platinum / therapeutic use
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Platinum