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Investigational New Drugs

, Volume 32, Issue 4, pp 746–752 | Cite as

A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer

  • Arun A. Azad
  • Emma K. Beardsley
  • Sebastian J. Hotte
  • Susan L. Ellard
  • Lawrence Klotz
  • Joseph Chin
  • Christian Kollmannsberger
  • Som D. Mukherjee
  • Kim N. ChiEmail author
PHASE II STUDIES

Summary

Purpose To investigate the efficacy and safety of combining vandetanib, an orally available multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR), with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods This was an open-label, randomized phase II multi-center study. Eligible patients had rising PSA on androgen deprivation therapy, minimal symptoms and were chemotherapy-naïve. Protocol therapy was either vandetanib 300 mg oral daily plus bicalutamide 50 mg oral daily (Arm A) or bicalutamide 50 mg oral daily alone (Arm B) with cross-over to vandetanib monotherapy at progression. The primary endpoint was PSA response (≥ 50 % decline from baseline). Results Thirty-nine patients were recruited, 19 in Arm A and 20 in Arm B. PSA response was comparable in Arm A and Arm B (18 vs. 19 %). Time to PSA progression was 3.16 months (95 % confidence interval (CI): 1.09, not reached (NR)) for Arm A and 3.09 months (95 % CI: 1.22, NR) for Arm B. Treatment discontinuation due to adverse events was more common in Arm A compared to Arm B (42 vs. 5 %; p = 0.019). Treatment with vandetanib was associated with a reduction in soluble VEGFR-2 levels after two cycles but an increase in plasma VEGF levels. Conclusion The combination of vandetanib and bicalutamide was associated with considerable toxicity and did not have superior efficacy over bicalutamide alone. Further evaluation of this combination is not warranted in mCRPC.

Keywords

Vandetanib Bicalutamide VEGFR-2 EGFR Castration-resistant prostate cancer 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Arun A. Azad
    • 1
  • Emma K. Beardsley
    • 1
  • Sebastian J. Hotte
    • 2
  • Susan L. Ellard
    • 3
  • Lawrence Klotz
    • 4
  • Joseph Chin
    • 5
  • Christian Kollmannsberger
    • 1
  • Som D. Mukherjee
    • 2
  • Kim N. Chi
    • 1
    • 6
    Email author
  1. 1.British Columbia Cancer AgencyVancouver Cancer CentreVancouverCanada
  2. 2.Juravinski Cancer CentreHamiltonCanada
  3. 3.British Columbia Cancer AgencyCentre for the Southern InteriorKelownaCanada
  4. 4.Sunnybrook Health Sciences CentreTorontoCanada
  5. 5.London Health Sciences CentreLondonCanada
  6. 6.Department of Medical OncologyBC Cancer AgencyVancouverCanada

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