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Updated: Jun 23, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients
József Horti1, Anders Widmark, Arnulf Stenzl
1National Institute of Oncology, Budapest, Hungary. hortij@freemail.hu
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/m(2) every 3 weeks) and prednisolone (P; 2 x 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 >or=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.
Insights
Vandetanib combined with docetaxel and prednisolone did not improve prostate-specific antigen response in metastatic hormone-refractory prostate cancer. This combination therapy showed no efficacy benefit over placebo plus docetaxel and prednisolone.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Vandetanib is an oral anticancer drug targeting VEGFR, EGFR, and RET signaling pathways.
- Metastatic hormone-refractory prostate cancer (mHRPC) remains a challenging clinical condition with limited treatment options.
- Combination therapies are being explored to improve outcomes in mHRPC.
Purpose of the Study:
- To evaluate the efficacy and safety of vandetanib in combination with docetaxel and prednisolone for patients with mHRPC.
- To assess the impact of vandetanib on prostate-specific antigen (PSA) response and disease progression.
Main Methods:
- A randomized, double-blind, placebo-controlled study.
- 86 patients with mHRPC were randomized to receive either vandetanib (100 mg/day) or placebo.
- Both arms received docetaxel (75 mg/m(2) every 3 weeks) and prednisolone (2 x 5 mg/day).
Main Results:
- A significantly lower PSA response rate was observed in the vandetanib group (40%) compared to the placebo group (67%).
- The vandetanib combination showed a trend towards increased disease progression or death (65% vs. 60%).
- While overall adverse event incidence was similar, more patients in the vandetanib arm experienced permanent discontinuation due to adverse events (28% vs. 12%).
Conclusions:
- Vandetanib in combination with docetaxel and prednisolone did not demonstrate any efficacy benefit in patients with mHRPC.
- The safety profile of vandetanib was consistent with previous reports, with increased rates of hypertension and rash in the combination arm.
- Further investigation into vandetanib for mHRPC is not supported by these findings.
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