Lack of association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and pain improvement in patients with oral cancer.

Kim N Du,Carlos J Roldan,Andrew J Shepherd,Lei MS Fang,Irvin M Ma,Shubh Desai,Juan P Cata,Moran Amit

doi:10.3332/ecancer.2020.1121

Abstract

BackgroundThere is a growing body of literature implicating angiotensin II in the modulation of tumour-associated inflammation and pain. However, the impact of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) on pain and inflammation has not yet been studied in oral cancers. The objective is to investigate the role of ACEi and ARB pharmacotherapy on preoperative pain and inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), in patients with oral cancer.MethodsWe performed a retrospective study on patients who underwent oral cancer surgery. The Wilcoxon rank-sum test or Kruskal–Wallis analysis was used to evaluate differences in demographic, tumour-related and preoperative characteristics and amongst patients using ARBs, ACEis and no treatment. Multivariable analysis was fitted to estimate the effects of important covariates on severe preoperative pain.ResultsA total of 162 patients with oral malignancies were included in the study. After adjusting for significant covariates, patients with perineural invasion were found to have higher levels of pain (p = 0.0278). Similarly, patients taking ARBs were found to have lower levels of perineural invasion (p = 0.035). The analysis did not demonstrate a significant difference in pain levels when comparing ARBs or ACEis to the no treatment group (p = 0.250). Furthermore, the use of ARB or ACEi did not significantly alter preoperative NLR (p = 0.701) or MLR (p = 0.869).ConclusionsWhen compared to no treatment, ARBs and ACEis are not associated with significant analgesic effect or decreased inflammatory scores (NLR, PLR and MLR).

Highlights

Oral and lip cancers rank amongst the 15th most common malignancies worldwide [1]
Information collected from the electronic medical records included age, gender, body mass index (BMI), the American Society of Anaesthesiologist’s (ASA) physical classification, stage of disease, history of smoking, tumour location, presence of perineural invasion, neoadjuvant chemotherapy, preoperative analgesics, preoperative analgesic use and preoperative blood pressure pharmacotherapy (ACEi, angiotensin II receptor blockers (ARBs) and no treatment)
After excluding patients using analgesics preoperatively (n = 90), the analysis indicated that the proportion of subjects reporting moderate-to-severe pain was higher in the ARB (37%) group than in the two other cohorts of patients (ACEIs = 3% and none = 2%, p = 0.004)

Summary

Introduction

Oral and lip cancers rank amongst the 15th most common malignancies worldwide [1]. Approximately 550,050 patients in the world are diagnosed with oral cancers each year [1]. Oral cancers are more common amongst men, older age groups and those with cofactors such as tobacco and alcohol use [2]. This patient population is at risk for cardiovascular comorbidities. Pain is one of the most common complaints of patients with oral malignancies and can be present even before any cancer treatment has been initiated [8]. The impact of angiotensinconverting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) on pain and inflammation has not yet been studied in oral cancers. The objective is to investigate the role of ACEi and ARB pharmacotherapy on preoperative pain and inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), in patients with oral cancer

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Discussion

Conclusion