SUMMARY: The objective of NRG Oncology RTOG 0123 was to test the ability of the angiotensin converting enzyme inhibitor (ACEI) captopril to reduce pulmonary damage after radiation for lung cancer. Despite significant effort, the trial did not analyze a sufficient number of patients to test the hypothesis due to early study closure. However, it did show the safety of the ACEI mitigation approach and the use of newer ACEIs, started during radiotherapy, may solve the accrual problems. OBJECTIVES: The primary objective of NRG Oncology RTOG 0123 was to test the ability of the angiotensin converting enzyme inhibitor (ACEI) captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. METHODS: Eligible patients included Stage II-IIIB non-small cell lung cancer, Stage I central NSCLC, or limited-stage small-cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for one year. The captopril was to be escalated to 50 mg TID. Primary endpoint was incidence of Grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: 81 patients were accrued between 6/2003 and 8/2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent prior to randomization and 40 patients were not randomized post-radiation. Major reasons for non-randomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of Grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSION: Despite significant resources and multiple amendments, NRG Oncology RTOG 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer ACEIs started during radiotherapy may solve the accrual problems.
