Randomized double-blind placebo-controlled trial evaluating pregabalin for chronic cough in patients with lung cancer.
Authors: Noronha Vanita , Menon Nandini Sharrel , Patil Vijay Maruti , Shah Minit Jalan , Joshi Amit , Jain Srushti , Nawale Kavita Prakash , Surve Rohan , Bafna Gunj , Jogdhankar Shweta , Shelar Priyanka , Singh Ashish , Salian Sushmita , Jadhav Pundlik , Shah Hetakshi , Mer Neha Jagdish , Vohra Ananya , Majumdar Swaratika , Badwe Rajendra A. , Prabhash Kumar 
Published: June 2024

LBA12082 Background: Chronic cough is a distressing symptom that detracts from the quality of life (QoL) of patients with cancer. Developing effective therapies for cough is an unmet need, with no approved medicines available. Neuromodulators like pregabalin may act centrally as cough suppressants. Methods: Randomized double-blind placebo-controlled study in the Department of Medical Oncology at Tata Memorial Hospital (Mumbai, India) in patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) with at least 2 weeks history of moderate or severe cough. Patients had ECOG PS 0-2, and creatinine clearance > 60 mL/min. Randomization was 1:1 to pregabalin 300 mg orally daily or matching placebo, both administered for 9 weeks. Primary endpoint was the difference in cough severity as measured by Visual Analog Scale (VAS) after 9 weeks treatment with pregabalin versus placebo. Secondary endpoints included cough severity on day 7 and week 9 measured by VAS, and Manchester Cough in Lung Cancer Scale (MCLCS); side-effects, and QoL assessed by EORTC QLQ C30 and LC13. Means of the change from baseline scores were calculated for patients in each arm, and compared between two arms by independent samples Mann Whitney U test. P < 0.05 was considered significant. Results: Between Jul 2022 and Dec 2023, we enrolled 166 patients: 83 to each arm. Median age was 56 years (IQR, 47-62.5); 112 (67.5%) were male, and 149 (89.8%) had metastatic NSCLC. Baseline cough severity was grade 2 in 127 (76.5%) and grade 3 in 37 (22.6%); median cough duration was 163 days. The therapy (pregabalin/placebo) was well tolerated in both arms, with no difference in grade > 3 toxicities between the two arms; P=0.908. Systemic cancer-directed therapy was started in 95.2% and 91.4% of patients in the pregabalin and placebo arms, respectively; P=0.328. By week 9, subjective improvement in cough was reported by 45 (57%) patients in pregabalin arm, and 40 (52.6%) patients in placebo arm; P=0.846. The mean VAS score (in mm) decreased from 71.58 at baseline, to 45.32 at day 7, and 19.73 by week 9 in the pregabalin arm; corresponding values in the placebo arm were 71.74, 46.23, and 21.18, respectively; P=0.530. Cough assessment by mean MCLCS scores showed a similar decrease throughout the course of the study, with no statistically significant differences between the two arms (Pregabalin-Baseline: 27.63, Day 7: 23.49, Week 9: 17.39; Placebo-Baseline: 27.28, Day 7: 23, Week 9: 17.34); P=0.455. There was no significant difference in QoL between the two arms. Mean LCCO (cough symptom question on QLQ LC13) score decreased from 75.9 (baseline) to 54.2 (day 7) to 36.4 (week 9) in pregabalin arm, vs 66.3, 54, and 31.4, respectively, in placebo arm; P=0.150. Conclusions: Pregabalin does not lead to a significant decrease in cough in patients with lung cancer. Systemic cancer-directed therapy is the most effective antitussive therapy for cancer-induced cough. Clinical trial information: CTRI/2020/11/029275 .