A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer

József Horti, Anders Widmark, Arnulf Stenzl, Miriam H. Federico, Raymond P. Abratt, Nick Sanders, Gillian M. Pover, I. Bodrogi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Vandetanib (ZACTIMA™) is a once-daily oral anticancer drug that selectively inhibits vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection signaling. This randomized (1:1), double-blind study evaluated vandetanib (100 mg/day) or placebo in combination with docetaxel (D; 75 mg/m2 every 3 weeks) and prednisolone (P; 2 × 5 mg/day) in 86 patients with metastatic hormone-refractory prostate cancer (mHRPC). The primary assessment was prostate-specific antigen (PSA) response (confirmed reduction of ≥50% from baseline) and a greater number of patients showed a PSA response with placebo + DP (67%) versus vandetanib + DP (40%); hazard ratio = 2.23 (one-sided 80% confidence limit = 2.90; one-sided p = 0.99). More patients experienced progression events (disease progression or death from any cause) with vandetanib + DP (65%) versus placebo + DP (60%); hazard ratio = 1.13 (one-sided 80% confidence limit = 1.44; one-sided p = 0.67). The overall incidence of adverse events was similar in both groups, although more patients experienced adverse events, leading to permanent discontinuation with vandetanib + DP (28%) versus placebo + DP (12%). However, the safety and tolerability profile for vandetanib was similar to that previously reported; adverse events that occurred more frequently in the vandetanib + DP arm were hypertension (14% vs. 2%), erythematous rash (14% vs. 2%), and exfoliative rash (12% vs. 2%). In this study of patients with mHRPC, vandetanib + DP did not demonstrate any efficacy benefit, compared with placebo + DP.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalCancer Biotherapy and Radiopharmaceuticals
Volume24
Issue number2
DOIs
Publication statusPublished - Apr 1 2009

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docetaxel
Prednisolone
Prostatic Neoplasms
Placebos
Hormones
Prostate-Specific Antigen
Exanthema
Vascular Endothelial Growth Factor Receptor
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Double-Blind Method
Epidermal Growth Factor Receptor
Transfection
Disease Progression

Keywords

  • Combination
  • Docetaxel
  • Hormone-refractory prostate cancer
  • Prednisolone
  • Vandetanib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology

Cite this

A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer. / Horti, József; Widmark, Anders; Stenzl, Arnulf; Federico, Miriam H.; Abratt, Raymond P.; Sanders, Nick; Pover, Gillian M.; Bodrogi, I.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 24, No. 2, 01.04.2009, p. 175-180.

Research output: Contribution to journalArticle

Horti, József ; Widmark, Anders ; Stenzl, Arnulf ; Federico, Miriam H. ; Abratt, Raymond P. ; Sanders, Nick ; Pover, Gillian M. ; Bodrogi, I. / A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer. In: Cancer Biotherapy and Radiopharmaceuticals. 2009 ; Vol. 24, No. 2. pp. 175-180.
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