title: Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma.
abstract: OBJECTIVE
  Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor.
  
  
  METHODS
  Adult patients with advanced MM were entered on a multicenter phase II study.
  
  
  RESULTS
  Twenty-seven patients (median age 69, range 39-79), median 4 (0-10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m(2) twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for >/==" BORDER="0">4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n = 7) compared with patients with progressive disease (n = 5). Overall median survival was 42 weeks (range 3-92+).
  
  
  CONCLUSIONS
  Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.
authors.affiliation: University of Arkansas for Medical Sciences, The Multiple Myeloma Institute for Research and Therapy, Little Rock, Arkansas, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Alison
authors.initials: A
authors.lastname: Stopeck
authors.forename: Alyssa
authors.initials: A
authors.lastname: Morimoto
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lancet
authors.forename: Maureen
authors.initials: M
authors.lastname: Cooper
authors.forename: Alison
authors.initials: A
authors.lastname: Hannah
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Stephan
authors.initials: S
authors.lastname: Faderl
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Julie
authors.initials: J
authors.lastname: Cherrington
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use*; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013792:Thalidomide / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2