title: Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001).
abstract: OBJECTIVE
  Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy.
  
  
  METHODS
  Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate.
  
  
  RESULTS
  Sixty-seven patients were enrolled. The median age was 64, and 66% (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20%; N = 13), fatigue (17%; N = 11), abdominal pain (17%; N = 11), and elevated alkaline phosphatase (15%; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29% (95% CI 18-41%) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28% of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug.
  
  
  CONCLUSIONS
  Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.
authors.affiliation: Banner MD Anderson Cancer Center, 1900 N. Higley Road, Gilbert, AZ, 85234, USA, Tomislav.dragovich@bannerhealth.com.
authors.forename: T
authors.initials: T
authors.lastname: Dragovich
authors.forename: D
authors.initials: D
authors.lastname: Laheru
authors.forename: F
authors.initials: F
authors.lastname: Dayyani
authors.forename: V
authors.initials: V
authors.lastname: Bolejack
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Seng
authors.forename: H
authors.initials: H
authors.lastname: Burris
authors.forename: P
authors.initials: P
authors.lastname: Rosen
authors.forename: M
authors.initials: M
authors.lastname: Hidalgo
authors.forename: P
authors.initials: P
authors.lastname: Ritch
authors.forename: A F
authors.initials: AF
authors.lastname: Baker
authors.forename: N
authors.initials: N
authors.lastname: Raghunand
authors.forename: J
authors.initials: J
authors.lastname: Crowley
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010793:Phthalazines / Q000008:administration & dosage; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D010793:Phthalazines; D011725:Pyridines; D003841:Deoxycytidine; C404768:vatalanib; D000093542:Gemcitabine