Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer: Results From NRG Oncology RTOG 0123.
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.
William
W
Small
NRG Oncology Statistics and Data Management Center, Philadelphia, PA.
Jennifer L
JL
James
Columbus Community Clinical Oncology Program, Columbus.
Timothy D
TD
Moore
Division of Cardiology, Northwestern University Hospital, Chicago, IL.
Dan J
DJ
Fintel
Blanchard Valley Radiation Oncology, Findlay, OH.
Stephen T
ST
Lutz
Department of Radiation Oncology, Henry Ford Health System, Detroit.
Benjamin
B
Movsas
University of Maryland, Baltimore, MD.
Mohan
M
Suntharalingam
Radiation Oncology Division, Mayo Clinic, Rochester, MN.
Yolanda I
YI
Garces
Newark Beth Israel Medical Center, Newark, NJ.
Robert
R
Ivker
Medical College of Wisconsin, Milwaukee, WI.
John
J
Moulder
NRG Oncology Statistics and Data Management Center, Philadelphia, PA.
Stephanie
S
Pugh
H. Lee Moffitt Cancer Center, Tampa, FL.
Lawrence B
LB
Berk
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011788:Quality of Life; D011832:Radiation Injuries / Q000188:drug therapy* / Q000209:etiology; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000209:etiology; D020266:Radiotherapy, Conformal / Q000009:adverse effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril