Chest
Volume 157, Issue 6, June 2020, Pages 1647-1655
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Thoracic Oncology: Original Research
Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial

https://doi.org/10.1016/j.chest.2019.11.048Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects.

Trial Registry

Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in

Section snippets

Trial Design

We conducted the trial at Tata Memorial Center (TMC), a tertiary oncology teaching hospital in Mumbai, India. The study was approved by the institutional ethics committee (Institutional Ethics Committee-II of Tata Memorial Center, project 1841) and monitored by the data safety monitoring subcommittee. All patients provided written informed consent. The trial was conducted according to principles laid down by the International Conference on Harmonization Good Clinical Practice guidelines,

Patients

Between June 2017 and June 2018, we randomized 128 patients, 64 to each arm. Details of patient enrollment, allocation, therapy, and analysis are provided in Figure 1. Pertinent demographics and baseline information are included in Table 1.

Therapy for Cough

Patients in both arms received physician’s choice of cough medication; in addition, patients in the aprepitant arm received aprepitant. For any patient whose cough was not controlled, another antitussive could be added. Cough medications used were

Discussion

To the best of our knowledge, ours is the first randomized trial to demonstrate the benefit of a cough medication in patients with advanced lung cancer. Aprepitant improved cough in patients with advanced lung cancer as evidenced by a significant decrease in cough severity and cough impact. This improvement was also seen in the cough domain of the QoL. The decrease in the cough parameters occurred as early as day 3 and continued to decrease at subsequent time points, until day 12, the end of

Conclusions

Aprepitant led to a significant improvement in cough in patients with advanced lung cancer, with no increase in severe side effects. Aprepitant represents a new treatment option for cough in patients with lung cancer.

Acknowledgments

Author contributions: V. N. and K. P. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. V. N., A. B., V. M. P., A. J., N. M., S. S., S. K., S. A. M., K. M., S. I., and K. P. contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the

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    Mr Maske is currently at the Marine Medical Services (Mumbai, India); Dr Ishi is currently at the NIMS Hospital (Nashik, India); the Khandesh Cancer Center (Dhule, India), and the Apex Wellness Hospital (Nashik, India).

    FUNDING/SUPPORT: This work was supported by an intramural grant from the Tata Memorial Center Research Administrative Council (TRAC), a grant from the Indian Co-operative Oncology Network, and an unrestricted educational grant from Glenmark Pharmaceuticals Ltd.

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