This project will test the effect of nicorandil to mitigate the lung damage that can occur as a side effect of radiation therapy for lung cancer. Thousands of veterans develop lung cancer every year, and are treated by radiation therapy. Studies of lung radiation injury in laboratory animals show that with nicorandil, investigators can significantly reduce the severity of lung fibrosis and heart toxicity.1,2 Nicorandil is FDA approved and in common use for treatment of angina. These studies will advance that work to human use. Successful mitigation of lung radiation damage and heart toxicity will improve the quality of life in veterans and non-veterans who are treated for lung cancer by radiation, and may also improve cure rates of radiation therapy for lung cancer.

Inclusion Criteria:

1. Histologically or cytologically-proven NSCLC; mixed histology with small cell lung carcinoma (SCLC) component not allowed
2. Patients with stage II - IV NSCLC who received at least 54 Gy of total planned thoracic radiation dose will be eligible; patients must have received at least one cycle of chemotherapy concurrently during the course of thoracic radiation; regimens allowed are platinum combinations with either etoposide or a taxane regardless of histology subtype; platinum with pemetrexed for patients with nonsquamous NSCLC only; patients with oligometastatic stage IV cancer are eligible if they have received only one line of systemic therapy for their stage IV cancer prior to the concurrent chemoradiation phase
3. Patient must have had a CR/PR/SD, 4-6 weeks after completing last fraction of chemotherapy / radiation therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 at the time of randomization
5. Absolute neutrophil count (ANC) >= 1,500/uL
6. Platelet count >= 100,000/uL
7. Hemoglobin >= 9 g/dL
8. Total bilirubin =< 1.5 times upper limit of normal (ULN) OR direct bilirubin normal (per institute standards)
9. Aspartate aminotransferase (AST) =< 1.5 x ULN; alanine aminotransferase (ALT) and AST =< 3 x ULN is acceptable if there is liver metastasis
10. Fertile patients must use adequate contraception

Exclusion Criteria:

1. Whole-brain radiotherapy (WBRT) < 14 days from the anticipated start of nicorandil/placebo administration
2. Unable to start nicorandil/placebo treatment between 4 - 6 weeks after completing the last dose of thoracic radiation
3. Active untreated brain or leptomeningeal metastases; in patients with treated central nervous system (CNS) metastases, eligible if symptoms controlled for at least 4 weeks; dexamethasone allowed if total daily dose does not exceed 2 mg
4. Major injuries or surgery (e.g., craniotomy) < 28 days from the start of nicorandil/placebo administration; wound should be healed prior to starting therapy
5. Second malignancies are allowed as long as the disease does not require active treatment with concomitant systemic cytotoxic chemotherapy, investigational or biologic therapy (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] or human epidermal growth factor receptor 2 [HER2] monoclonal antibodies); hormone-related therapies (e.g., gonadotrophin releasing hormone (LHRH) agonists, tamoxifen, etc.) are allowed
6. Concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would increase the risk associated with study participation and/or limit compliance with study requirements
7. Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher proteinuria
8. Systemic therapy or investigational agent administered < 28 days prior to treatment with nicorandil
9. Pregnancy or breast feeding; female patients with child-bearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin [B-HCG] test in urine or serum) prior to commencing study treatment
10. Creatinine > 1.5 x ULN or creatinine clearance levels (CrCL) < 45 mL/min
11. Centrally located tumors with radiographic evidence (computed tomography [CT] or magnetic resonance imaging [MRI]) of local invasion of major blood vessels
12. acute myocardial infarction within 2 weeks before percutaneous coronary intervention
13. contraindications to treatment with nicorandil (allergy, glaucoma, digestive ulcer, is currently taking phosphodiesterase-5 inhibitor)
14. bypass restenosis
15. PCI history
16. hypotension
17. impaired liver function
18. renal insufficiency requiring hemodialysis
19. pregnancy
20. connective tissue disease
21. life expectancy ≤ 12 months
22. left main coronary artery disease
23. bypass graft lesion and lesions unsuitable for OCT
24. unwillingness or inability to provide informed consent