title: A randomized, double-blind, placebo-controlled phase II study of vandetanib plus docetaxel/prednisolone in patients with hormone-refractory prostate cancer.
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.
authors.affiliation: National Institute of Oncology, Budapest, Hungary. hortij@freemail.hu
authors.forename: József
authors.initials: J
authors.lastname: Horti
authors.forename: Anders
authors.initials: A
authors.lastname: Widmark
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Federico
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Abratt
authors.forename: Nick
authors.initials: N
authors.lastname: Sanders
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Pover
authors.forename: István
authors.initials: I
authors.lastname: Bodrogi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D010880:Piperidines; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D011239:Prednisolone; D017430:Prostate-Specific Antigen; C452423:vandetanib