title: Clinical analysis of patients treated with afatinib for advanced non-small cell lung cancer: A Nagano Lung Cancer Research Group observational study.
abstract: BACKGROUND
  Afatinib has been available in Japan for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) since May 2014. We conducted an observational study in patients treated with afatinib in Nagano prefecture, focusing on response and associated toxicities.
  
  
  METHODS
  We analyzed the clinical records of NSCLC patients treated with afatinib between May 2014 and February 2015.
  
  
  RESULTS
  The records of a total of 73 patients (27 men, 46 women) with a median age of 69 years (range: 42-85 years) were analyzed. Afatinib was administered to 11 patients as a first-line therapy, but it was predominantly administered as a fifth-line or beyond therapy (32 cases, 43.8%). The overall response rates for afatinib as a first-line therapy and beyond second-line therapy were 80% (95% confidence interval [CI]: 55.2-100.0%) and 27.1% (95% CI: 14.5-39.7%), respectively. The main toxicities grade >3 included diarrhea (8.2%), skin rash (6.8%), nausea (6.8%), and appetite loss (6.8%). A low body surface area (BSA) (<1.5m2) was significantly associated with a higher frequency of diarrhea grade >2, compared with a higher BSA (≥ 1.5m2). Forty-eight patients (63.0%) were treated without a dose reduction of afatinib.
  
  
  CONCLUSIONS
  Although the survival benefit with afatinib remains unclear, our observational analysis demonstrated the feasibility of using afatinib for EGFR-mutated NSCLC in clinical practice. In particular, a relatively high level of drug delivery is possible. In addition, a lower BSA may be a predictor of diarrhea in patients treated with afatinib.
authors.affiliation: Department of Pulmonary Diseases, Nagano Red Cross Hospital, Nagano City, Japan; First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto City, Japan. Electronic address: spdf4zz9@sand.ocn.ne.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Department of Pulmonary Diseases, Nagano Red Cross Hospital, Nagano City, Japan. Electronic address: koyama@nagano-med.jrc.or.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Koyama
authors.affiliation: Department of Pulmonary Diseases, Nagano Red Cross Hospital, Nagano City, Japan. Electronic address: hirokura1@hotmail.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuraishi
authors.affiliation: Department of Pulmonary Diseases, Nagano Matsushiro General Hospital, Nagano City, Japan. Electronic address: tmiyahar@hotmail.com.
authors.forename: Takashige
authors.initials: T
authors.lastname: Miyahara
authors.affiliation: Department of Pulmonary Diseases, Nagano Municipal Hospital, Nagano City, Japan. Electronic address: fumiaki_yoshiike@hospital.nagano.nagano.jp.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yoshiike
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Shinshu Ueda Medical Center, Ueda City, Japan. Electronic address: t.agatuma@nagano-hosp.go.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Agatsuma
authors.affiliation: Division of Thoracic Surgery, Saku Central Hospital Advanced Care Center, Saku City, Japan. Electronic address: yamamoto.ryohei@sakuhp.or.jp.
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Treatment Center, Aizawa Hospital, Matsumoto City, Japan. Electronic address: ai.70477@ai-hosp.or.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Pulmonary Diseases, Matsumoto Medical Center, Matsumoto City, Japan. Electronic address: m_tos@me.com.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pulmonary Diseases, Suwa Red Cross Hospital, Suwa City, Japan. Electronic address: t-hachiya@suwa.jrc.or.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hachiya
authors.affiliation: Department of Medical Oncology, Iida Municipal Hospital, Iida City, Japan; Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine, Matsumoto City, Japan. Electronic address: daisuke2705@gmail.com.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Gomi
authors.affiliation: First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto City, Japan. Electronic address: tateishi@shinshu-u.ac.jp.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tateishi
authors.affiliation: First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto City, Japan. Electronic address: masayuki@shinshu-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.affiliation: Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine, Matsumoto City, Japan. Electronic address: tomonobu@shinshu-u.ac.jp.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Koizumi
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D001830:Body Surface Area; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D000077716:Afatinib; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cytotoxic chemotherapy; Diarrhea; Epidermal growth factor receptor-tyrosine kinase inhibitors; Skin rash; Toxicity