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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 (100mg/day) or placebo in combination with docetaxel (D; 75mg/m² every 3 weeks) and prednisolone (P; 2×5mg/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.