title: An open label, multicenter, phase II study of dovitinib in advanced thyroid cancer.
abstract: BACKGROUND
  This phase 2 study investigated the efficacy and safety of dovitinib (TKI258), a receptor tyrosine kinase inhibitor with potent activity against fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), in locally advanced or metastatic thyroid cancer patients.
  
  
  METHODS
  Patients with advanced thyroid cancer that was refractory or not appropriate for (131)I received dovitinib orally, 500mg once daily for five consecutive days, followed by a 2-day rest every week. The primary end-point was objective response rate. Secondary end-points were progression-free survival (PFS), overall survival (OS), duration of response, changes in tumour markers and safety.
  
  
  RESULTS
  Between January 2013 and October 2014, a total of 40 patients were enrolled. There were 23 (57.5%) papillary thyroid cancer, 12 (30%) medullary thyroid cancer and 5 (12.5%) follicular thyroid cancer patients. One patient had withdrawn consent before the administration of dovitinib. The overall response rate was 20.5% (8/39) and disease control rate was 69.1% (26/39). Median PFS was 5.4 months (95% confidence interval (CI), 2.0-8.8) and median OS was not reached with 8.4 months follow-up duration. Common treatment-related adverse events were diarrhoea (53.8%), anorexia (35.8%), vomiting (25.6%), fatigue (23%) and nausea (20.5%), most of which were grade 1 or 2. There were no grade 4 events or treatment-related deaths. Dose interruption occurred in 12 (30.7%) patients, and 19 (48.7%) patients experienced dose reduction due to adverse events.
  
  
  CONCLUSIONS
  Dovitinib has a modest activity with manageable toxicity in locally advanced or metastatic thyroid cancer.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woong Youn
authors.initials: WY
authors.lastname: Chung
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kee-Hyun
authors.initials: KH
authors.lastname: Nam
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Gangnam Severance Hospital, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang Regional Cancer Center, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Hoon-Gu
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Division of Hematology-Oncology, Pusan National University Yangsan Hospital, Busan, Republic of Korea.
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Republic of Korea.
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: NOBELG@yuhs.ac.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cbc1971@yuhs.ac.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: C500007:4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D015363:Quinolones; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Dovitinib; Efficacy; Phase 2; Safety; Thyroid cancer