Journal Article

A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study)

Yokouchi, Hiroshi, Kuwano, Kazuyoshi, Tsuboi, Masahiro, Sakai, Shuji, Azuma, Arata, Katakami, Nobuyuki, Yoshino, Ichiro, Sakamoto, Kazuhiro, Yamashita, Yoshinori, Takenoyama, Mitsuhiro, Iwasawa, Tae, Okada, Morihito, Asato, Yuji, Fukuoka, Junya, Tada, Hirohito, Yoshida, Shigetoshi, Okubo, Kenichi, Hiroshima, Kenzo, Okami, Jiro, Nakagawa, Kazuhiko, Nakanishi, Yoichi, Yamashita, Motohiro, Chida, Masayuki, Ikeda, Norihiko, Iwata, Takekazu, Mitsudomi, Tetsuya, Matsuura, Motoki, Tomii, Keisuke, Yoshimura, Kenichi

2016

Overview

Background 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. 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. Methods Pirfenidone 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. Results From 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. Conclusions Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. Trial registration This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (Registration Number: UMIN000007774 ).

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group
• Subject: Administration, Oral / Biomedical research / Cancer therapies / Care and treatment / Chemotherapy / Clinical trials / Complications and side effects / Computer centers / Disease Progression / Drug Administration Schedule / Drug dosages / Hospitals / Humans / Idiopathic Pulmonary Fibrosis - diagnostic imaging / Idiopathic Pulmonary Fibrosis - drug therapy / Idiopathic Pulmonary Fibrosis - mortality / Idiopathic Pulmonary Fibrosis - pathology / Japan / Lung cancer / Lung diseases / Lung Neoplasms - diagnostic imaging / Lung Neoplasms - mortality / Lung Neoplasms - pathology / Lung Neoplasms - surgery / Medicine / Medicine & Public Health / Mortality / Oncology / Ostomy / Pneumology/Respiratory System / Pneumonectomy - adverse effects / Pneumonia / Pulmonary fibrosis / Pyridones - administration & dosage / Pyridones - adverse effects / Risk Factors / Surgery / Thoracic surgery / Time Factors / Treatment Outcome