title: Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer.
abstract: BACKGROUND
  RET fusions were recently identified in non-small cell lung cancer (NSCLC) and are considered as a potential therapeutic target of NSCLC. Sorafenib, a multi-kinase inhibitor, has potent anti-RET activity. We conducted a study to evaluate the efficacy of sorafenib in a small number of patients with RET fusion-positive NSCLC.
  
  
  METHODS
  Eligible patients had advanced or recurrent NSCLC, were more than 20 years old, had undergone treatment with one or more previous chemotherapy regimens, had an Eastern Cooperative Oncology Group performance status 0-2, had adequate organ function, and provided informed consent. The presence of the RET fusion gene was confirmed by a split FISH assay. The patients were treated twice daily with 400mg of sorafenib taken orally. The treatment was continued until either disease progression or unacceptable toxicity.
  
  
  RESULTS
  From March 2012 to April 2013, three patients were enrolled. The responses to sorafenib included one patient with stable disease (SD) and two patients with progressive disease (PD). One patient took sorafenib for twelve months. The most common toxicities were palmar-plantar erythrodysesthesia syndrome, hypertension, and diarrhea.
  
  
  CONCLUSIONS
  Since sorafenib did not show dramatic responses, we suggest testing other RET inhibitors for the treatment of RET fusion-positive NSCLC. This study was registered at UMIN as trial number 000007515.
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Horiike
authors.affiliation: Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uenami
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Tanimoto
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Kaburaki
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tambo
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yanagitani
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Ohyanagi
authors.affiliation: Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.affiliation: Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Horai
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ward, Tokyo 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D000077157:Sorafenib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D051096:Proto-Oncogene Proteins c-ret
keywords: Non-small cell lung cancer; RET; Sorafenib