title: Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC.
  
  
  METHODS
  Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
  
  
  RESULTS
  Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups.
  
  
  CONCLUSIONS
  Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.
authors.affiliation: Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Division of Hematology and Oncology, Chang-Gung Memorial Hospital Linkou, Linkou, Taiwan.
authors.forename: Tsai-Sheng
authors.initials: TS
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.affiliation: Division of Hematology and Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Ruey-Kuen
authors.initials: RK
authors.lastname: Hsieh
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Yu
authors.affiliation: Division of Hematology and Oncology, Chie-Mei Medical Center Yong-Kang Branch, Tainan, Taiwan.
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hwang
authors.affiliation: Division of Gastroenterology, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Tsai-Yuan
authors.initials: TY
authors.lastname: Hsieh
authors.affiliation: Division of Hematology and Oncology, Chie-Mei Medical Center Liouying Branch, Tainan, Taiwan.
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Huang
authors.affiliation: Cancer Treatment Center, Taipei Veterans General Hospital, Taiwan.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.affiliation: AstraZeneca, Taipei, Taiwan.
authors.forename: Robin
authors.initials: R
authors.lastname: Meng
authors.affiliation: Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000187:drug effects; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib