A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naive 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 Chi

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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-naive. 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.
Original languageEnglish
Pages (from-to)746-752
Number of pages7
JournalInvestigational New Drugs
Volume32
Issue number4
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Cite this

Azad, Arun A ; Beardsley, Emma K ; Hotte, Sebastian J ; Ellard, Susan L ; Klotz, Lawrence ; Chin, Joseph ; Kollmannsberger, Christian ; Mukherjee, Som D ; Chi, Kim N. / A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naive castration-resistant prostate cancer. In: Investigational New Drugs. 2014 ; Vol. 32, No. 4. pp. 746-752.
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title = "A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naive castration-resistant prostate cancer",
abstract = "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-naive. 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.",
author = "Azad, {Arun A} and Beardsley, {Emma K} and Hotte, {Sebastian J} and Ellard, {Susan L} and Lawrence Klotz and Joseph Chin and Christian Kollmannsberger and Mukherjee, {Som D} and Chi, {Kim N}",
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A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naive castration-resistant prostate cancer. / Azad, Arun A; Beardsley, Emma K; Hotte, Sebastian J; Ellard, Susan L; Klotz, Lawrence; Chin, Joseph; Kollmannsberger, Christian; Mukherjee, Som D; Chi, Kim N.

In: Investigational New Drugs, Vol. 32, No. 4, 08.2014, p. 746-752.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naive castration-resistant prostate cancer

AU - Azad, Arun A

AU - Beardsley, Emma K

AU - Hotte, Sebastian J

AU - Ellard, Susan L

AU - Klotz, Lawrence

AU - Chin, Joseph

AU - Kollmannsberger, Christian

AU - Mukherjee, Som D

AU - Chi, Kim N

PY - 2014/8

Y1 - 2014/8

N2 - 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-naive. 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.

AB - 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-naive. 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.

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DO - 10.1007/s10637-014-0091-8

M3 - Article

VL - 32

SP - 746

EP - 752

JO - Investigational New Drugs

JF - Investigational New Drugs

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ER -