TY - JOUR
T1 - Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221)
T2 - A Pilot Double-Blind Randomized Trial
AU - Sio, Terence T.
AU - Atherton, Pamela J.
AU - Pederson, Levi D.
AU - Zhen, W. Ken
AU - Mutter, Robert W.
AU - Garces, Yolanda I.
AU - Ma, Daniel J.
AU - Leenstra, James L.
AU - Rwigema, Jean-Claude M.
AU - Dakhil, Shaker
AU - Bearden, James D.
AU - van der Veen, Sonja J.
AU - Ganti, Apar K.
AU - Schild, Steven E.
AU - Miller, Robert C.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Purpose: Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis.Methods and Materials: We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20 mg of lisinopril or placebo once daily during and up to 3 months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer TherapyeLung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with c 2 and Kruskal-Wallis testing.Results: Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5 years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, PConclusions: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safetydand possibly beneficial by limited PRO measuresdin concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future. (C) 2018 Published by Elsevier Inc.
AB - Purpose: Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis.Methods and Materials: We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20 mg of lisinopril or placebo once daily during and up to 3 months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer TherapyeLung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with c 2 and Kruskal-Wallis testing.Results: Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5 years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, PConclusions: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safetydand possibly beneficial by limited PRO measuresdin concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future. (C) 2018 Published by Elsevier Inc.
KW - CONVERTING ENZYME-INHIBITORS
KW - QUALITY-OF-LIFE
KW - SYMPTOMATIC RADIATION PNEUMONITIS
KW - RISK
KW - RADIOTHERAPY
KW - CONCURRENT
KW - REDUCE
KW - RATS
KW - ACE
U2 - 10.1016/j.ijrobp.2018.10.035
DO - 10.1016/j.ijrobp.2018.10.035
M3 - Article
SN - 0360-3016
VL - 103
SP - 686
EP - 696
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 3
ER -