Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer.MethodsPirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non–AE-IPF rate during postoperative days 0–30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee.ResultsFrom June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7–99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5–99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3–5 adverse events were observed.ConclusionsPerioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients.Trial registrationThis clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (Registration Number: UMIN000007774).
Highlights
Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery
Patients were ineligible if they had a history of previous thoracotomy/video-assisted thoracoscopic surgery; history of IPF treatment; history of radiation therapy that included a lung in the treatment field or chemotherapy; other known causes of interstitial pneumonia; severe comorbidities; history of drug allergy; or obvious history of acute exacerbation of IPF
Among the full-analysis set (FAS) cases, two patients stopped pirfenidone administration before surgery due to patient request, and surgery was cancelled for one patient because metastatic lesions were identified on further examination
Summary
Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. Life-threatening acute exacerbation (AE) of IPF (AE-IPF) may occur in association with cancer treatment, including radiotherapy, chemotherapy, and surgery, thereby severely restricting the therapeutic options for IPF-associated lung cancer. Several treatments, including intraoperative fluid balance control [7], postoperative ulinastatin [8], and preoperative methylpredonisolone and sivelestat [9], have been reported to have the potential to prevent postoperative AE; these were all evaluated in small, single-institute prospective or retrospective studies. A Japanese multi-institutional retrospective large cohort study revealed that none of the potential prophylactic treatments tested, including steroids, sivelestat, and ulinastatin, demonstrated an ability to prevent AE [10]
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