title: Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer.
abstract: BACKGROUND
  Although CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC.
  
  
  METHODS
  One hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety.
  
  
  RESULTS
  No statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab.
  
  
  CONCLUSIONS
  Combining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.
authors: Department of Medicine, Indiana University Simon Cancer Center, Indianapolis, IN. Electronic address: bhoneil@iupui.edu.
authors: Bert H
authors: BH
authors: O'Neil
authors: Department of Oncology, Institutul Oncologic, Cluj-Napoca, Romania.
authors: Calin
authors: C
authors: Cainap
authors: Clinical Digestive Oncology, University Hospital Gasthuisberg/Leuven, Leuven, Belgium.
authors: Eric
authors: E
authors: Van Cutsem
authors: Russian Academy of Medical Sciences, Moscow, Russia.
authors: Vera
authors: V
authors: Gorbunova
authors: Department of Medical Oncology, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors: Christos S
authors: CS
authors: Karapetis
authors: Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN.
authors: Jordan
authors: J
authors: Berlin
authors: Department of Medicine, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH.
authors: Richard M
authors: RM
authors: Goldberg
authors: AbbVie Inc, North Chicago, IL.
authors: Qin
authors: Q
authors: Qin
authors: AbbVie Inc, North Chicago, IL.
authors: Jiang
authors: J
authors: Qian
authors: AbbVie Inc, North Chicago, IL.
authors: Justin L
authors: JL
authors: Ricker
authors: AbbVie Inc, North Chicago, IL.
authors: JuDee
authors: J
authors: Fischer
authors: AbbVie Inc, North Chicago, IL.
authors: Mark D
authors: MD
authors: McKee
authors: AbbVie Inc, North Chicago, IL.
authors: Dawn M
authors: DM
authors: Carlson
authors: Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Tae Won
authors: TW
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D007191:Indazoles / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010671:Phenylurea Compounds / Q000008:administration & dosage; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D000068258:Bevacizumab; C513486:linifanib; D002955:Leucovorin; D005472:Fluorouracil
keywords: ABT-869; Advanced colorectal cancer; Colon cancer; Second-line; TKI