title: Incidence and clinical features of drug-induced lung injury in patients with advanced colorectal cancer receiving cetuximab: results of a prospective multicenter registry.
abstract: OBJECTIVE
  We investigated the incidence and clinical features of drug-induced lung injury during cetuximab therapy in Japanese patients with colorectal cancer in a prospective multicenter registry based on a central registration system.
  
  
  METHODS
  We investigated and followed up patients with or suspected of having drug-induced lung injury among 2006 patients with cetuximab-treated colorectal cancer. A subcommittee of medical oncologists, pulmonologists and a radiologist evaluated and discussed each case of drug-induced lung injury that occurred during cetuximab therapy.
  
  
  RESULTS
  Sixty-six patients were identified and further examinations of drug-induced lung injury were conducted during the registration period. We analyzed time to onset, patient characteristics and factors associated with mortality. Cetuximab-related drug-induced lung injury occurred in 24 (1.2%) patients, and was rated as Grade 3 or worse in 15 (0.7%) patients. Fourteen patients received steroid pulse therapy. Ten patients with drug-induced lung injury died, of whom eight received steroid pulse therapy. The incidence of drug-induced lung injury was significantly higher in elderly patients, and in patients with prior interstitial lung disease. There was no particular trend in the time to onset. Patients with early onset of drug-induced lung injury (within 90 days) after starting cetuximab therapy had higher mortality than patients with later onset (over 90 days).
  
  
  CONCLUSIONS
  The incidence of drug-induced lung injury in cetuximab-treated patients was 1.2%. Because drug-induced lung injury is potentially serious, it is important to promptly initiate appropriate treatments. Considering that early onset drug-induced lung injury during cetuximab therapy is associated with a poor prognosis, close monitoring is mandatory for these patients.
authors.affiliation: Department of Medical Oncology, Kinki University, Osakasayama, Osaka Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka taroh@cfs.med.osaka-u.ac.jp.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Pulmonary Medicine, Infection Disease and Oncology Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Fukujuji Hospital, Kiyose, Tokyo.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Diagnostic Imaging, Saitama Medical University International Medical Center, Hidaka, Saitama.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Sakai
authors.affiliation: Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Saitama.
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgical Oncology, The University of Tokyo, Bunkyo-ku, Tokyo.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.affiliation: Merck Serono Co. Ltd, Meguro-ku, Tokyo.
authors.forename: Shogo
authors.initials: S
authors.lastname: Inoshiri
authors.affiliation: Bristol-Myers K.K., Shinjuku-ku, Tokyo.
authors.forename: Makiko
authors.initials: M
authors.lastname: Izawa
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: Misawa City Hospital, Misawa, Aomori, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000556:secondary; D055370:Lung Injury / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D015398:Signal Transduction / Q000187:drug effects; D014057:Tomography, X-Ray Computed
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: biological therapy; cetuximab; chemotherapy; colorectal cancer; drug-induced lung injury