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, W Ken 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 K Ganti, Steven E Schild, Robert C Miller
Author Information
Terence T Sio: Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona. Electronic address: Sio.Terence@mayo.edu.
Pamela J Atherton: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Levi D Pederson: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
W Ken Zhen: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska.
Robert W Mutter: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Yolanda I Garces: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Daniel J Ma: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
James L Leenstra: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Jean-Claude M Rwigema: Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona.
Shaker Dakhil: Department of Radiation Oncology, Cancer Center of Kansas, Wichita, Kansas.
James D Bearden: Department of Radiation Oncology, Spartanburg Medical Center, Spartanburg, South Carolina.
Sonja J van der Veen: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Apar K Ganti: Division of Oncology-Hematology, Department of Internal Medicine, VA Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska.
Steven E Schild: Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona.
Robert C Miller: Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida.
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 χ 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.
