Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial
| Autor: | Martin Schlumberger, Massimo Santoro, Rossella Elisei, Barbara Jarzab, Eric Baudin, Peter Langmuir, Samuel A. Wells, Henning Dralle, James Vasselli, Anderson J. Ryan, Jessica Read, Robert F. Gagel, Bruce G. Robinson, James A. Fagin |
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| Přispěvatelé: | S. A., Well, B. G., Robinson, R. F., Gagel, H., Dralle, J. A., Fagin, Santoro, Massimo, E., Baudin, R., Elisei, B., Jarzab, J. R., Vasselli, J., Read, P., Langmuir, A. J., Ryan, M. J., Schlumberger |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Cabozantinib adverse effects/therapeutic use Thyroid Neoplasm Vandetanib drug therapy/pathology Metastasis Thyroid carcinoma Disease Progression Double-Blind Method Female Humans Male Middle Aged Neoplasm Metastasis Piperidine Placebos chemistry.chemical_compound Double-Blind Method Piperidines adverse effects/therapeutic use Placebos Quinazoline Medicine Humans Epidermal growth factor receptor Thyroid Neoplasms Neoplasm Metastasis Thyroid cancer biology business.industry Cancer Medullary thyroid cancer Middle Aged medicine.disease Carcinoma Neuroendocrine Oncology chemistry Cancer research biology.protein Disease Progression Quinazolines Female business medicine.drug |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 30(2) |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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 and Methods Patients with advanced MTC were randomly assigned in a 2:1 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). |
| Databáze: | OpenAIRE |
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