title: Tocilizumab, a proposed therapy for the cachexia of Interleukin6-expressing lung cancer.
abstract: BACKGROUND
  We previously reported the role of IL-6 in a murine model of cancer cachexia and currently documented a patient in whom tocilizumab, anti-IL-6 receptor antibody, dramatically improved cachexia induced by IL-6 over-expressing lung cancer. Despite this potential to alleviate cancer cachexia, tocilizumab has not been approved for this clinical use. Therefore, preceding our planned clinical trial of tocilizumab, we designed the two studies described here to evaluate the levels of IL-6 in patients with lung cancer and the effect of tocilizumab in a murine model of human cancer cachexia.
  
  
  METHODS
  First, we measured serum IL-6 levels in patients with lung cancer and analyzed its association with cachexia and survival. Next, we examined the effect of a rodent analog of tocilizumab (MR16-1) in the experimental cachexia model.
  
  
  RESULTS
  Serum IL-6 levels were higher in patients with cachexia than those without cachexia. In patients with chemotherapy-resistant lung cancer, a high IL-6 serum level correlated strongly with survival, and the cut-off level for affecting their prognosis was 21 pg/mL. Meanwhile, transplantation of IL-6-expressing Lewis Lung Carcinoma cells caused cachexia in mice, which then received either MR16-1 or 0.9% saline. Tumor growth was similar in both groups; however, the MR16-1 group lost less weight, maintained better food and water intake and had milder cachectic features in blood. MR16-1 also prolonged the survival of LLC-IL6 transplanted mice (36.6 vs. 28.5 days, p = 0.016).
  
  
  CONCLUSIONS
  Our clinical and experimental studies revealed that serum IL-6 is a surrogate marker for evaluating cachexia and the prognosis of patients with chemotherapy resistant metastatic lung cancer and that tocilizumab has the potential of improving prognosis and ameliorating the cachexia that so devastates their quality of life. This outcome greatly encourages our clinical trials to evaluate the safety and efficacy of tocilizumab treatment for patients with increased serum IL-6.
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Takahashi
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Respiratory Internal Medicine, Kameda Medical Center, Kamogawa-City, Chiba, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kaneko
authors.affiliation: Fukuoka Clinic, Adachi-Ku, Tokyo, Japan.
authors.forename: Tokuhide
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.affiliation: Shien-lab, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Koizumi
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Higashiosaka City, Osaka, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.affiliation: Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D002100:Cachexia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab