The primary objective of NRG Oncology Radiation Therapy Oncology Group 0123 was to test the ability of the angiotensin-converting enzyme inhibitor 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.
Eligible patients included stage II-IIIB non–small cell lung cancer, stage I central non–small cell lung cancer, or limited-stage small cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for 1 year. The captopril was to be escalated to 50 mg three times a day. Primary endpoint was incidence of grade 2+ radiation-induced pulmonary toxicity in the first year.
Eighty-one patients were accrued between June 2003 and August 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 before randomization and 40 patients were not randomized postradiation. Major reasons for nonrandomization 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.
Despite significant resources and multiple amendments, NRG Oncology Radiation Therapy Oncology Group 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 angiotensin-converting enzyme inhibitors started during radiotherapy may solve the accrual problems.
*Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University
†NRG Oncology Statistics and Data Management Center, Philadelphia, PA
‡Columbus Community Clinical Oncology Program, Columbus
§Division of Cardiology, Northwestern University Hospital, Chicago, IL
∥Blanchard Valley Radiation Oncology, Findlay, OH
¶Department of Radiation Oncology, Henry Ford Health System, Detroit
#University of Maryland, Baltimore, MD
**Radiation Oncology Division, Mayo Clinic, Rochester, MN
††Newark Beth Israel Medical Center, Newark, NJ
‡‡Medical College of Wisconsin, Milwaukee, WI
§§H. Lee Moffitt Cancer Center, Tampa, FL
Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI) Cancer Institute.
Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, Chicago, IL, 2009.
T.D.M. reports a current consultancy for BMS. D.J.F. reports past grants to institution for work under consideration for publication. S.T.L. reports royalties from Wiley Publishers. B.M. reports current grant to institution from ACR/RTOG for work under consideration for publication, current support for travel from ACR/RTOG for role of QOL Chair for work under consideration for publication, and current and pending grants from Varian and Philips for research unrelated to this study. J.M. reports past grants to institution from RTOG for work under consideration for publication, past grants to J.M. and his institution from NIH outside the submitted work, and pending grant to institution from the VA outside the submitted work. S.P. reports a past grant from the PA Department of Health. The other authors declare no conflicts of interest.
Reprints: William Small Jr, MD, FASTRO, Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160S 1st Ave, Maguire Center, Rm 2932, Maywood, IL 60153. E-mail: firstname.lastname@example.org.