aprepitant and Cough

Cough is mediated by vagal afferent fibres innervating the larynx and proximal airways. Pre-clinical studies suggest that vagal C fibres produce Substance P, one of the tachykinin family of neuropeptides, which has been shown to enhance cough via the neurokinin-1 (NK-1) receptor and studies in animal models have also shown that NK-1 antagonists are effective at blocking induced cough. In the past, tachykinin receptor antagonists have yielded disappointing results in treating asthma and cough, however most of the activity of the agents tested was restricted to the peripheral nervous system and also the outcomes measures evaluating cough not optimal. More recently a small proof of concept study has suggest that aprepitant, an NK-1 antagonist licensed for the prevention of chemotherapy induced nausea and vomiting, might have beneficial effects on cough frequency in patients with lung cancer. In this review we investigate the current evidence for the anti-tussive effect of these therapies and the clinical trials in progress.

Topics: Animals; Antitussive Agents; Aprepitant; Cough; Humans; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1

Topics: Aged; Antitussive Agents; Aprepitant; Cough; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vagus Nerve Stimulation

Although cough is a common and distressing symptom in patients with lung cancer, there is almost no evidence to guide treatment. Aprepitant, a centrally acting neurokinin-1 inhibitor, significantly decreased cough frequency in a pilot study.. Patients with advanced lung cancer and cough lasting over 2 weeks despite a cough suppressant were randomized 1:1 to aprepitant 125 mg orally on day 1 and then 80 mg orally on days 2 to 7 with physician's choice of antitussive; or to physician's choice of antitussive alone. Evaluation was at baseline and on days 3, 7, 9, and 12. The primary end point was subjective cough improvement on day 9, measured by the Visual Analog Scale and Manchester Cough in Lung Cancer Scale. Secondary end points included quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Lung Cancer-Specific Quality of Life Questionnaire and toxicity.. Between 2017 and 2018, 128 patients were randomized. Median baseline cough duration was 90 days. Mean Visual Analog Scale scores (in mm) at baseline and day 9 were 68 and 39 in the aprepitant arm and 62 and 49 in the control arm, respectively (P < .001); mean Manchester Cough in Lung Cancer Scale scores at baseline and day 9 were 33 and 23 in the aprepitant arm and 30 and 25 in the control arm, respectively (P < .001). Overall QoL was not significantly different between the two arms; however, aprepitant led to a significant improvement in the cough-specific QoL domain (P = .017). Aprepitant did not increase severe adverse events.. Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects.. Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in.

Topics: Adult; Aged; Aprepitant; Carcinoma, Non-Small-Cell Lung; Cough; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neurokinin-1 Receptor Antagonists; Pilot Projects; Treatment Outcome; Young Adult

Topics: Antitussive Agents; Aprepitant; Cough; Humans; Lung Neoplasms; Receptors, Neurokinin-1