Why Use Aprepitant Only as a Cough Suppressant in Lung Cancer When at Higher Doses it Could Also Exert an Antitumor Action?

Abstract

Effective antitussive cough treatments are an important need in patients with lung cancer LC Aprepitant drug a selective neurokinin-1 receptor NK-1R antagonist and used for the treatment of nausea vomiting blocks the activation of the receptor by substance P SP this activation also mediates cough 1 Two randomized trials have clearly shown that aprepitant day 1 125 mg 2 7 2 3 80 mg suppresses cough in LC patients 1 2 Preclinical clinical studies have also shown the involvement of the SP NK-1R system in cancer progression and the potential use of aprepitant as a new antitumor drug has been suggested 3 The keypoints ofthese studies are the following LC cells synthesize release SP which acts through autocrine paracrine and neuroendocrine tumor mass mechanisms LC tumor mass increases SP level in lung and blood compared to healthy subjects SP plasma levels are higher in subjects with cough and in patients with cancer SP increases both cough and the proliferation of LC cells LC cells overexpress the NK-1R this receptor is involved in the viability of these cells in a concentration-dependent manner NK-1R antagoFig 1 Lung cancer LC patients substance P SP via the neurokinin-1 receptor NK-1R promotes cough and tumor progression The NK-1R antagonist aprepitant could exert a dual therapeutic effect in these patients cough suppressant and antitumor action nists including aprepitant suppress cough and exert an antitumor action because they decrease LC cell proliferation and induce the death of LC cells by apoptosis.