title: Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors.
abstract: OBJECTIVE
  CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors.
  
  
  METHODS
  Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1.
  
  
  RESULTS
  Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m(2)/day (n=3), 2 mg/m(2)/day (n=3), 3.3 mg/m(2)/day (n=3), 5 mg/m(2)/day (n=3), 7 mg/m(2)/day (n=3), 9 mg/m(2)/day (n=6), and 12 mg/m(2)/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m(2)/day. The MTD was determined as 12 mg/m(2)/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days).
  
  
  CONCLUSIONS
  This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m(2)/day on D1 and D8 every 3 weeks.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Department of Internal Medicine, Kangbuk Samsung Medical Center, Seoul, Korea.
authors.forename: Yun Gyoo
authors.initials: YG
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001577:Benzophenones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; C552333:N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide; D014633:Valine
keywords: CKD-516; Phase I clinical trial; Solid tumor; Vascular disrupting agent