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.
Written by:
Azad AA, Beardsley EK, Hotte SJ, Ellard SL, Klotz L, Chin J, Kollmannsberger C, Mukherjee SD, Chi KN. Are you the author?
British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada.
Reference: Invest New Drugs. 2014 Mar 28. Epub ahead of print.
doi: 10.1007/s10637-014-0091-8
PubMed Abstract
PMID: 24671507
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