Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer: Results From NRG Oncology RTOG 0123

William Small, Jennifer L. James, Timothy D. Moore, Dan J. Fintel, Stephen T. Lutz, Benjamin Movsas, Mohan Suntharalingam, Yolanda Isabel Garces, Robert Ivker, John Moulder, Stephanie Pugh, Lawrence B. Berk

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

OBJECTIVES:: 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. MATERIALS AND METHODS:: 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. RESULTS:: 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. CONCLUSIONS:: 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.

Original languageEnglish (US)
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
DOIs
StateAccepted/In press - Apr 20 2016

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Captopril
Angiotensin-Converting Enzyme Inhibitors
Lung Neoplasms
Radiation
Radiotherapy
Lung
Radiation Oncology
Random Allocation
Non-Small Cell Lung Carcinoma
Incidence
Observation
Safety
Quality of Life
Cytokines
Physicians

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer : Results From NRG Oncology RTOG 0123. / Small, William; James, Jennifer L.; Moore, Timothy D.; Fintel, Dan J.; Lutz, Stephen T.; Movsas, Benjamin; Suntharalingam, Mohan; Garces, Yolanda Isabel; Ivker, Robert; Moulder, John; Pugh, Stephanie; Berk, Lawrence B.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, 20.04.2016.

Research output: Contribution to journalArticle

Small, William ; James, Jennifer L. ; Moore, Timothy D. ; Fintel, Dan J. ; Lutz, Stephen T. ; Movsas, Benjamin ; Suntharalingam, Mohan ; Garces, Yolanda Isabel ; Ivker, Robert ; Moulder, John ; Pugh, Stephanie ; Berk, Lawrence B. / Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer : Results From NRG Oncology RTOG 0123. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2016.
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abstract = "OBJECTIVES:: 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. MATERIALS AND METHODS:: 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. RESULTS:: 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. CONCLUSIONS:: 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.",
author = "William Small and James, {Jennifer L.} and Moore, {Timothy D.} and Fintel, {Dan J.} and Lutz, {Stephen T.} and Benjamin Movsas and Mohan Suntharalingam and Garces, {Yolanda Isabel} and Robert Ivker and John Moulder and Stephanie Pugh and Berk, {Lawrence B.}",
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T1 - Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer

T2 - Results From NRG Oncology RTOG 0123

AU - Small, William

AU - James, Jennifer L.

AU - Moore, Timothy D.

AU - Fintel, Dan J.

AU - Lutz, Stephen T.

AU - Movsas, Benjamin

AU - Suntharalingam, Mohan

AU - Garces, Yolanda Isabel

AU - Ivker, Robert

AU - Moulder, John

AU - Pugh, Stephanie

AU - Berk, Lawrence B.

PY - 2016/4/20

Y1 - 2016/4/20

N2 - OBJECTIVES:: 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. MATERIALS AND METHODS:: 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. RESULTS:: 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. CONCLUSIONS:: 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.

AB - OBJECTIVES:: 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. MATERIALS AND METHODS:: 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. RESULTS:: 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. CONCLUSIONS:: 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.

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