Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.
J Clin Oncol
; 30(2): 134-41, 2012 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-22025146
ABSTRACT
PURPOSE:
There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. PATIENTS ANDMETHODS:
Patients with advanced MTC were randomly assigned in a 21 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.RESULTS:
Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%).CONCLUSION:
Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Quinazolinas
/
Neoplasias da Glândula Tireoide
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos