Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial

Terence T. Sio, Pamela J. Atherton, Levi D. Pederson, Weining Zhen, Robert W. Mutter, Yolanda I. Garces, Daniel J. Ma, James L. Leenstra, Jean Claude M. Rwigema, Shaker Dakhil, James D. Bearden, Sonja J. van der Veen, Apar Kishor P Ganti, Steven E. Schild, Robert C. Miller

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)686-696
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume103
Issue number3
DOIs
StatePublished - Mar 1 2019

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Lisinopril
lungs
Lung Neoplasms
cancer
Placebos
Lung
Radiotherapy
cough
Cough
Dyspnea
radiation therapy
Thorax
anaphylaxis
Angioedema
hypotension
dyspnea
Anaphylaxis
enzyme inhibitors
angiotensins
Angiotensin-Converting Enzyme Inhibitors

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221) : A Pilot Double-Blind Randomized Trial. / Sio, Terence T.; Atherton, Pamela J.; Pederson, Levi D.; Zhen, Weining; Mutter, Robert W.; Garces, Yolanda I.; Ma, Daniel J.; Leenstra, James L.; Rwigema, Jean Claude M.; Dakhil, Shaker; Bearden, James D.; van der Veen, Sonja J.; Ganti, Apar Kishor P; Schild, Steven E.; Miller, Robert C.

In: International Journal of Radiation Oncology Biology Physics, Vol. 103, No. 3, 01.03.2019, p. 686-696.

Research output: Contribution to journalArticle

Sio, TT, Atherton, PJ, Pederson, LD, Zhen, W, Mutter, RW, Garces, YI, Ma, DJ, Leenstra, JL, Rwigema, JCM, Dakhil, S, Bearden, JD, van der Veen, SJ, Ganti, AKP, Schild, SE & Miller, RC 2019, 'Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial', International Journal of Radiation Oncology Biology Physics, vol. 103, no. 3, pp. 686-696. https://doi.org/10.1016/j.ijrobp.2018.10.035
Sio, Terence T. ; Atherton, Pamela J. ; Pederson, Levi D. ; Zhen, Weining ; Mutter, Robert W. ; Garces, Yolanda I. ; Ma, Daniel J. ; Leenstra, James L. ; Rwigema, Jean Claude M. ; Dakhil, Shaker ; Bearden, James D. ; van der Veen, Sonja J. ; Ganti, Apar Kishor P ; Schild, Steven E. ; Miller, Robert C. / Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221) : A Pilot Double-Blind Randomized Trial. In: International Journal of Radiation Oncology Biology Physics. 2019 ; Vol. 103, No. 3. pp. 686-696.
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abstract = "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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AU - Sio, Terence T.

AU - Atherton, Pamela J.

AU - Pederson, Levi D.

AU - Zhen, Weining

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 Kishor P

AU - Schild, Steven E.

AU - Miller, Robert C.

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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.

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