title: Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience.
abstract: BACKGROUND
  Being overweight has been reported to induce hepatic dysfunction during cytotoxic chemotherapy. Severe hepatic dysfunction can also be observed during gefitinib monotherapy, leading to interrupted or discontinued treatment. However, whether being overweight is a risk factor during gefitinib therapy is unknown.
  
  
  METHODS
  We retrospectively reviewed 183 Japanese patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor-naïve non-small cell lung cancer (NSCLC) harboring EGFR mutations, who received gefitinib monotherapy between July 2007 and February 2014. We defined being overweight as having a body mass index (BMI) ≥ 25 kg/m2and assessed its potential relationship with ≥grade 2 hepatic dysfunction.
  
  
  RESULTS
  The patient demographics were as follows: 114 women; median age 72 years (range 42-95 years); BMI ≥ 25 kg/m2, n = 32; performance status 0-1, n = 136; stage IIIB/IV, n = 141; and major EGFR mutations, n = 171. Hepatic dysfunction ≥grade 2 during the gefitinib therapy was observed in 44 (24.0 %) patients, 22 (50.0 %) of whom interrupted or discontinued treatment. The median duration from gefitinib administration to the development of hepatic dysfunction was 56 days (range 6-1,352 days). Overweight patients were more likely to develop hepatic dysfunction ≥grade 2 compared to non-overweight patients according to a multivariate analysis adjusted for several confounding factors (hazard ratio 2.24; 95 % confidence interval 1.01-4.95; p = 0.046).
  
  
  CONCLUSIONS
  These results suggest that being overweight may induce hepatic dysfunction during gefitinib monotherapy in Japanese patients with EGFR-mutated NSCLC.
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Naohiro
authors: N
authors: Oda
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. khotta@okayama-u.ac.jp.|Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan. khotta@okayama-u.ac.jp.
authors: Katsuyuki
authors: K
authors: Hotta
authors: Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan.
authors: Hiroshige
authors: H
authors: Yoshioka
authors: Department of Respiratory Medicine, National Hospital Organization Iwakuni Medical Center, Iwakuni, Japan.
authors: Kenichiro
authors: K
authors: Kudo
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Eiki
authors: E
authors: Ichihara
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Yuka
authors: Y
authors: Kato
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Kiichiro
authors: K
authors: Ninomiya
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Daisuke
authors: D
authors: Minami
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Takashi
authors: T
authors: Ninomiya
authors: Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
authors: Toshio
authors: T
authors: Kubo
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Kadoaki
authors: K
authors: Ohashi
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Akiko
authors: A
authors: Sato
authors: Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors: Nagio
authors: N
authors: Takigawa
authors: Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
authors: Masahiro
authors: M
authors: Tabata
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Mitsune
authors: M
authors: Tanimoto
authors: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors: Katsuyuki
authors: K
authors: Kiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D044466:Asian People; D015992:Body Mass Index; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008111:Liver Function Tests; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D050177:Overweight / Q000150:complications*; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR-tyrosine kinase inhibitor; Gefitinib; Hepatic dysfunction; Lung cancer; Overweight