Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial
Introduction Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to r...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-10-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/10/e060619.full |
| _version_ | 1811192598593798144 |
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| author | Cheng Chen Yong Yang Mingqiang Kang Zhihua Li Benhua Xu Chun Chen Bangwei Zeng Dan Xue Rongxiang Cao Siqin Liao |
| author_facet | Cheng Chen Yong Yang Mingqiang Kang Zhihua Li Benhua Xu Chun Chen Bangwei Zeng Dan Xue Rongxiang Cao Siqin Liao |
| author_sort | Cheng Chen |
| collection | DOAJ |
| description | Introduction Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy.Methods and analysis This study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention.Ethics and dissemination This study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.Trial registration number ChiCTR2100043032. |
| first_indexed | 2024-04-11T23:56:22Z |
| format | Article |
| id | doaj.art-63790bd1a0e54e4cbe2bee894f3faa6e |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-11T23:56:22Z |
| publishDate | 2022-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-63790bd1a0e54e4cbe2bee894f3faa6e2022-12-22T03:56:22ZengBMJ Publishing GroupBMJ Open2044-60552022-10-01121010.1136/bmjopen-2021-060619Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trialCheng Chen0Yong Yang1Mingqiang Kang2Zhihua Li3Benhua Xu4Chun Chen5Bangwei Zeng6Dan Xue7Rongxiang Cao8Siqin Liao9Department of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Oncology Department, The Second Hospital of Zhangzhou, Zhangzhou, People`s Republic of ChinaDepartment of Radiation Oncology, Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological, and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaNosocomial Infection Control Branch, Fujian Medical University Union Hospital, Fuzhou, ChinaPulmonary Department, Fujian Medical University Union Hospital, Fuzhou, ChinaPulmonary Department, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of PET/CT Center, Fujian Medical University Union Hospital, Fuzhou, ChinaIntroduction Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy.Methods and analysis This study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention.Ethics and dissemination This study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.Trial registration number ChiCTR2100043032.https://bmjopen.bmj.com/content/12/10/e060619.full |
| spellingShingle | Cheng Chen Yong Yang Mingqiang Kang Zhihua Li Benhua Xu Chun Chen Bangwei Zeng Dan Xue Rongxiang Cao Siqin Liao Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial BMJ Open |
| title | Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial |
| title_full | Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial |
| title_fullStr | Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial |
| title_full_unstemmed | Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial |
| title_short | Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial |
| title_sort | pirfenidone for the prevention of radiation induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma a protocol for a randomised controlled trial |
| url | https://bmjopen.bmj.com/content/12/10/e060619.full |
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