Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 2, pp 379–387

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001)

  • T. Dragovich
  • D. Laheru
  • F. Dayyani
  • V. Bolejack
  • L. Smith
  • J. Seng
  • H. Burris
  • P. Rosen
  • M. Hidalgo
  • P. Ritch
  • A. F. Baker
  • N. Raghunand
  • J. Crowley
  • D. D. Von Hoff
Original Article

Abstract

Purpose

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.

Conclusion

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.

Keywords

Vatalinib Pancreatic adenocarcinoma Tyrosine kinase inhibitor Second-line treatment 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • T. Dragovich
    • 1
    • 2
  • D. Laheru
    • 3
  • F. Dayyani
    • 1
  • V. Bolejack
    • 4
  • L. Smith
    • 5
  • J. Seng
    • 6
  • H. Burris
    • 7
  • P. Rosen
    • 8
  • M. Hidalgo
    • 9
  • P. Ritch
    • 10
  • A. F. Baker
    • 2
  • N. Raghunand
    • 2
  • J. Crowley
    • 4
  • D. D. Von Hoff
    • 11
  1. 1.Banner MD Anderson Cancer CenterGilbertUSA
  2. 2.The University of Arizona Cancer CenterTucsonUSA
  3. 3.Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins UniversityBaltimoreUSA
  4. 4.Cancer Research and BiostatisticsSeattleUSA
  5. 5.South Texas Oncology HematologySan AntonioUSA
  6. 6.Virginia Piper Cancer InstituteMinneapolisUSA
  7. 7.Sarah Cannon Cancer CenterNashvilleUSA
  8. 8.Tower Cancer Research FoundationBeverly HillsUSA
  9. 9.Spanish National Cancer Research Centre (CNIO)MadridSpain
  10. 10.Medical College of WisconsinMilwaukeeUSA
  11. 11.Virginia G. Piper Cancer Center at Scottsdale HealthcareScottsdaleUSA

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