Impact of Angiotensin I-converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC

Abstract

It has been shown that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can decrease tumor growth and tumor-associated angiogenesis and inhibit metastasis. Epidermal growth factor receptor (EGFR) mutations are found in approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) in East Asia and in 10–15% of such patients in Western countries. We retrospectively identified 228 patients with histologically confirmed advanced NSCLC and 73 patients with early stage disease; 103 of these patients took antihypertensive drugs, and 112 received treatment with EGFR tyrosine kinase inhibitors (TKIs). There was a significant difference in progression-free survival after first-line therapy (PFS1) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients treated with TKIs, there was a significant difference in PFS but not in overall survival (OS) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients with advanced NSCLC, there was a significant difference in PFS1 between the ACEI/ARB group and the non-ACEI/ARB group. ACEI/ARB in combination with standard chemotherapy or TKIs had a positive effect on PFS1 or OS, regardless of whether the lung cancer was in the early or advanced stage.

Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study

“… 47 Although limited studies have suggested improvements in survival in patients with lung cancer receiving renin-angiotensin system inhibitors and tyrosine kinase inhibitors or chemotherapy, the effect of ACEIs specifically on lung cancer progression remains uncertain. 48 49 …”

Targeting the renin-angiotensin system to improve cancer treatment: Implications for immunotherapy

“…Available clinical data suggest that RASi may potentiate the effect of certain systemic antitumor therapies. The use of RASi was associated with better outcomes in patients with different solid tumors who received platinum-based CHT ( 142 , 143 , 149 , 165 , 172 ). The gain in overall survival (OS; the length of time from either the date of diagnosis or the start of treatment that patients are still alive) ranged from ~3 months in advanced non–small cell lung cancer (NSCLC) to 5.7 months in advanced gastric cancer and even 11 months in metastatic colorectal cancer (CRC) ( 142 , 149 , 165 , 172 ).…”

“…Finally, two studies suggested a putative clinical benefit of RASi use in patients who received epidermal growth factor receptor (EGFR) TKIs ( 128 , 143 ). This could be explained by the preclinical finding that AT1R signaling can regulate proliferation and migration of cancer cells through transactivation of the EGFR by metalloproteinase-dependent shedding of EGF ligands ( 4 ).…”

The Angiotensin II Type 1 Receptor Antagonist Losartan Affects NHE1-Dependent Melanoma Cell Behavior

“…Remarkably, ATII treatment leads to a significant decrease in E-cadherin expression and an increase in the activity of matrix metalloprotease 9 (MMP9), and, notably, the AT1-mediated effects resemble changes characteristic of epithelial-mesenchymal transition (EMT) [6]. Conversely, the use of AT 1 receptor blockers in non-small cell lung cancer patients is associated with longer progression-free survival after first line therapy, while overall survival is hardly affected [7]. In advanced gastric cancer patients treated with platinum-based chemotherapeutics, the additional application of AT 1 receptor blockers improves survival [8], and, in patients with advanced pancreatic cancer, inhibition of AT 1 in combination with the administration of the cytostatic gemcitabine may improve the clinical outcome [9].…”