OBJECTIVE: To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). DATA SOURCES: Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. STUDY SELECTION AND DATA EXTRACTION: Two phase 2 trials and 1 phase 3 trial were identified. DATA SYNTHESIS: Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. CONCLUSIONS: Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.
OBJECTIVE: To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). DATA SOURCES: Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. STUDY SELECTION AND DATA EXTRACTION: Two phase 2 trials and 1 phase 3 trial were identified. DATA SYNTHESIS: Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. CONCLUSIONS: Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.
Authors: Juan Zhang; Dan Luo; Fang Li; Zhiyi Li; Xiaoli Gao; Jie Qiao; Lin Wu; Miaoling Li Journal: Oxid Med Cell Longev Date: 2021-10-07 Impact factor: 6.543