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.
N1 - Funding Information:
Research reported in this publication was supported by the Community Clinical Oncology Program Cancer Prevention and Symptom Intervention Pilot Project Fund (research base grant award number CA037447-28) and by the National Cancer Institute of the National Institutes of Health under the Award Number CA189823 to the Alliance for Clinical Trials in Oncology NCORP Research Base (Jan C. Buckner, MD, contact principal investigator). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2018
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 Therapy–Lung, 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 χ2 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, P <.05). Conclusions: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety—and possibly beneficial by limited PRO measures—in 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.
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 Therapy–Lung, 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 χ2 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, P <.05). Conclusions: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety—and possibly beneficial by limited PRO measures—in 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.
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U2 - 10.1016/j.ijrobp.2018.10.035
DO - 10.1016/j.ijrobp.2018.10.035
M3 - Article
C2 - 30395904
AN - SCOPUS:85059562050
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 -