title: A randomized, double-blind, phase IIa dose-finding study of Vandetanib (ZD6474) in Japanese patients with non-small cell lung cancer.
abstract: BACKGROUND
  Vandetanib (ZACTIMA) is a once-daily, oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling. Vandetanib was evaluated as a monotherapy in a randomized, double-blind, dose-finding study in Japan.
  
  
  METHODS
  Eligible patients with locally advanced or metastatic (stage IIIB/IV) or recurrent non-small cell lung cancer, previously treated with chemotherapy, were randomized to receive once-daily oral vandetanib 100, 200, or 300 mg (1:1:1). The primary objective was to determine the objective response rate for each vandetanib dose.
  
  
  RESULTS
  Fifty-three patients received vandetanib (100 mg, n = 17; 200 mg, n = 18; 300 mg, n = 18). The objective response rate in each dose arm was 17.6% (3 of 17; 100 mg), 5.6% (1 of 18; 200 mg), and 16.7% (3 of 18; 300 mg). Common adverse events included rash, diarrhea, hypertension, and asymptomatic QTc prolongation. The adverse event profile was generally consistent with that reported previously for agents that inhibit the VEGFR or EGFR signaling pathways. Among the three responders evaluated for EGFR mutation, two had no mutation, and in one case, the EGFR mutation status could not be determined by direct DNA sequencing and amplification refractory mutation system assay of EGFR exons 19-21. Baseline plasma VEGF levels appeared to be lower in patients who experienced clinical benefit after vandetanib treatment.
  
  
  CONCLUSIONS
  In Japanese patients with advanced non-small cell lung cancer, vandetanib monotherapy (100-300 mg/d) demonstrated antitumor activity with an acceptable safety and tolerability profile.
authors: Okayama Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan. kkiura@md.okayama-u.ac.jp
authors: Katsuyuki
authors: K
authors: Kiura
authors: Kazuhiko
authors: K
authors: Nakagawa
authors: Tetsu
authors: T
authors: Shinkai
authors: Kenji
authors: K
authors: Eguchi
authors: Yuichiro
authors: Y
authors: Ohe
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Masahiro
authors: M
authors: Tsuboi
authors: Soichiro
authors: S
authors: Yokota
authors: Takashi
authors: T
authors: Seto
authors: Haiyi
authors: H
authors: Jiang
authors: Kazuto
authors: K
authors: Nishio
authors: Nagahiro
authors: N
authors: Saijo
authors: Masahiro
authors: M
authors: Fukuoka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000453:epidemiology / Q000556:secondary; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000453:epidemiology / Q000556:secondary; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014408:Biomarkers, Tumor; D010880:Piperidines; D011799:Quinazolines; D066246:ErbB Receptors; C452423:vandetanib