title: 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).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients.
  
  
  
  This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).
authors.affiliation: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, Japan.
authors.forename: Takekazu
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, Japan. iyoshino@faculty.chiba-u.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.affiliation: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: First Department of Surgery, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Department of Thoracic Surgery, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.affiliation: Department of Thoracic Surgery, Ibaraki Prefectural Central Hospital, 6528, Kobuchi, Kasama, Ibaraki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Asato
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima minamicho, Chuo-ku, Kobe, Hyogo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Department of Respiratory Surgery, National Hospital Organization Yokohama Medical Center, 3-60-2 Harajuku, Totsuka-ku, Yokohama, Kanagawa, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Respiratory Surgery, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1, Aoyamacho, Kure, Hiroshima, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of General Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi Higashinari, Osaka, Osaka, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Okami
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, 377-2, Ohnohigashi, Sayama, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.affiliation: Department of Thoracic Surgery, Shikoku Cancer Center, 160, Minamiumemotomachiko, Matsuyama, Ehime, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1, Hikarigaoka, Fukushima, Fukushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Okubo
authors.affiliation: Department of Surgical Oncology, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Fukuoka Minami-ku, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.affiliation: Department of General Thoracic Surgery, Dokkyo Medical University, 880, Kitakobayashi, Shimotsugagun Mibumachi, Tochigi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Chida
authors.affiliation: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1, Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.affiliation: Department of Thoracic Surgery, Hiroshima City Hospital, 7-33, Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, 6-16-1, Tomiokahigashi, Kanazawa-ku, Yokohama, Kanagawa, Japan.
authors.forename: Tae
authors.initials: T
authors.lastname: Iwasawa
authors.affiliation: Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.affiliation: Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjyuku-ku, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 477-96, Ohwada-Shinden, Yachiyo, Chiba, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.affiliation: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki, Nagasaki, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.affiliation: Innovative Clinical Research Center, Kanazawa University Hospital, 13-1, Takaramachi, Kanazawa, Ishikawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Thoracic Surgery, Suita Tokushukai Hospital, 21-1, Senriokanishi, Osaka, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Medical Oncology, Kinki University School of Medicine, 377-2, Ohnohigashi, Sayama, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000284:Administration, Oral; D018450:Disease Progression; D004334:Drug Administration Schedule; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007564:Japan; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011013:Pneumonectomy / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011728:Pyridones; C093844:pirfenidone
keywords: Acute exacerbation; Idiopathic pulmonary fibrosis; Lung cancer; Pirfenidone; Surgery