Radiation Pneumonitis in Lung Cancer Patients - The Neglected Patient-Related Variables

Bezjak, Andrea; Soyfer, Viacheslav; Yi, Qijian; Sun, A.; Kane, Georgina; Waldron, J.; Cho, J.; Wells, W.; Payne, Debbie

doi:10.1016/j.ijrobp.2005.07.391

Cited by 6 publications

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“…Of these 45 patients 5 withdrew consent. Forty patients were not randomized post-radiation due to patients' refusal (11), physician preference (6), ineligibility for randomization (5), adverse event during RT (3), disease progression/death (4), or not specified (11). There were four patient deaths due to lung cancer in the observation arm; there was one patient death due to lung cancer and two patients lost to follow-up in the captopril arm.…”

Section: Resultsmentioning

confidence: 99%

“…The basic concept now has the active support of the National Cancer Institute (19), and there is a growing base of experimental (9-11) and clinical (9-12) evidence that supports the efficacy of this approach.…”

Section: Discussionmentioning

confidence: 99%

“…First, the newer generation of ACEIs are taken only once per day, and some of these ( e.g. , enalapril) have mitigation efficacy in experimental models at least as good as that found for captopril (5, 9,11). Second, as there is now strong experimental (20) and clinical (10-12) evidence that the use of ACEIs during cancer therapy is safe, ACEI dose escalation could be done before the end of radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent work has noted that the mitigation effect was a property of many different ACEIs (9-11). In addition, some recent clinical studies provide even stronger support for the concept behind the study, as both prospective (9) and retrospective (10-12) studies have shown evidence that ACEIs can decrease radiation-induced pulmonary injury.…”

Section: Introductionmentioning

confidence: 99%

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Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer

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James

Moore

et al. 2018

American Journal of Clinical Oncology

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer

Small

James

Moore

et al. 2018

American Journal of Clinical Oncology

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“…In contrast, Bezjak et al . ( 51 ) showed that similar treatment resulted in a decrease in the incidence of pneumonitis in irradiated lung cancer patients, from 29% (34/118) to 12.5% (3/24). A similar analysis found that incidental use of ACE inhibitors cuts pneumonitis occurrence in irradiated lung cancer patients from 11% (11/101) to 2% (1/61) ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Model Development and Use of ACE Inhibitors for Preclinical Mitigation of Radiation-Induced Injury to Multiple Organs

Medhora

Gao²,

Wu³

et al. 2014

Radiation Research

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The NIH/NIAID initiated a countermeasure program to develop mitigators for radiation-induced injuries from a radiological attack or nuclear accident. We have previously characterized and demonstrated mitigation of single organ injuries, such as radiation pneumonitis, pulmonary fibrosis or nephropathy by angiotensin converting enzyme (ACE) inhibitors. Our current work extends this research to examine the potential for mitigating multiple organ dysfunctions occurring in the same irradiated rats. Using total body irradiation (TBI) followed by bone marrow transplant, we tested four doses of X radiation (11, 11.25, 11.5 and 12 Gy) to develop lethal late effects. We identified three of these doses (11, 11.25 and 11.5 Gy TBI) that were lethal to all irradiated rats by 160 days to test mitigation by ACE inhibitors of injury to the lungs and kidneys. In this study we tested three ACE inhibitors at doses: captopril (88 and 176 mg/m2/day), enalapril (18, 24 and 36 mg/m2/day) and fosinopril (60 mg/m2/day) for mitigation. Our primary end point was survival or criteria for euthanization of morbid animals. Secondary end points included breathing intervals, other assays for lung structure and function and blood urea nitrogen (BUN) to assess renal damage. We found that captopril at 176 mg/m2/day increased survival after 11 or 11.5 Gy TBI. Enalapril at 18–36 mg/m2/day improved survival at all three doses (TBI). Fosinopril at 60 mg/m2/day enhanced survival at a dose of 11 Gy, although no improvement was observed for pneumonitis. These results demonstrate the use of a single countermeasure to mitigate the lethal late effects in the same animal after TBI.

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Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

Kharofa

Cohen

Tomic

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

113

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Radiation Pneumonitis in Lung Cancer Patients - The Neglected Patient-Related Variables

Cited by 6 publications

References 0 publications

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer

Utility of the ACE Inhibitor Captopril in Mitigating Radiation-associated Pulmonary Toxicity in Lung Cancer

Model Development and Use of ACE Inhibitors for Preclinical Mitigation of Radiation-Induced Injury to Multiple Organs

Decreased Risk of Radiation Pneumonitis With Incidental Concurrent Use of Angiotensin-Converting Enzyme Inhibitors and Thoracic Radiation Therapy

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