vandetanib
Sources réglementaires consultées
Indications approuvées
- Adultes, adolescents et enfants à partir de 5 ans atteints d’un cancer médullaire de la thyroïde muté RET, agressif et symptomatique, non résécable, localement avancé ou métastatique. Confirmer la mutation RET par un test validé avant traitement.
Contre-indications
Absolues
- Hypersensibilité au vandétanib ou aux excipients.
- Syndrome du QT long congénital ou QTc >480 ms.
- Utilisation concomitante d’arsenic, cisapride, érythromycine intraveineuse, torémifène, mizolastine, moxifloxacine ou antiarythmiques de classe IA ou III.
- Allaitement.
Mises en garde cliniques
- Peut allonger fortement le QTc et provoquer torsades ou mort subite. Réaliser ECG, potassium, calcium, magnésium et TSH avant traitement, aux semaines 1, 3, 6 et 12 puis tous les 3 mois ; ne pas débuter si QTc >480 ms et ne reprendre que lorsque QTc redevient <450 ms. — CIMA/AEMPS, ficha técnica 11749001
- Arrêter définitivement en cas de pneumopathie interstitielle confirmée ou de réaction cutanée sévère. Surveiller AVC ischémique, hémorragie, insuffisance cardiaque, diarrhée, hypertension, encéphalopathie postérieure réversible et cicatrisation ; suspendre au moins 1 mois avant chirurgie programmée. — OpenFDA, set_id e5721cb8-4185-47b9-bbb3-1c587e558a03
Interactions médicamenteuses
- SévèreMédicaments allongeant le QT
Mécanisme: Ils augmentent le risque d’allongement du QT, de torsades et de mort subite.
Recommandation: Ne pas utiliser les agents contre-indiqués et éviter les autres si possible ; sans alternative, surveiller étroitement ECG et électrolytes.
CIMA/AEMPS, ficha técnica 11749001
- SévèreInducteurs puissants du CYP3A4
Mécanisme: Ils réduisent l’exposition au vandétanib.
Recommandation: Éviter, y compris le millepertuis.
OpenFDA, set_id e5721cb8-4185-47b9-bbb3-1c587e558a03
- SévèreMetformine ou autres substrats d’OCT2
Mécanisme: Le vandétanib augmente l’exposition au substrat ; l’AUC de la metformine a augmenté de 74 %.
Recommandation: Surveiller la toxicité et envisager de réduire la dose du substrat.
CIMA/AEMPS, ficha técnica 11749001
- SévèreDigoxine et autres substrats de la P-gp
Mécanisme: Le vandétanib augmente l’exposition à la digoxine.
Recommandation: Contrôler les concentrations et la toxicité ; ajuster la dose si nécessaire.
CIMA/AEMPS, ficha técnica 11749001
Effets indésirables
Communs (≥1%)
diarrhée · éruption cutanée · nausées · hypertension · céphalées · allongement du QTc · diminution de l’appétit · hypocalcémie
Grossesse et allaitement
Peut nuire au fœtus. Vérifier l’absence de grossesse avant traitement. Les femmes et les hommes fertiles doivent utiliser une contraception pendant le traitement et au moins 4 mois après. Ne pas allaiter pendant le traitement ni pendant 4 mois après.
Bibliographie récente (PubMed)
Hantaviruses are a significant and emerging global public health threat, impacting more than 200,000 individuals worldwide each year. The single-stranded RNA viruses belong to the Hantaviridae family and are responsible for causing two acute febrile diseases in humans: Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). Currently, there are no licensed treatments or vaccines available globally for HTNV infection. Various candidate drugs have shown efficacy in increasing survival rates during the early stages of HTNV infection. Some of these drugs include lactoferrin, ribavirin, ETAR, favipiravir and vandetanib. Immunotherapy utilizing neutralizing antibodies (NAbs) generated from Hantavirus convalescent patients show efficacy against HTNV. Monoclonal antibodies such as MIB22 and JL16 have demonstrated effectiveness in protecting against HTNV infection. The development of vaccines and antivirals, used independently and/or in combination, is critical for elucidating hantaviral infections and the impact on public health. RNA interference (RNAi) arised as an emerging antiviral therapy, is a highly specific degrades RNA, with post-transcriptional mechanism using eukaryotic cells platform. That has demonstrated efficacy against a wide range of viruses, both in vitro and in vivo. Recent antiviral methods involve using small interfering RNA (siRNA) and other, immune-based therapies to target specific gene segments (S, M, or L) of the Hantavirus. This therapeutic approach enhances viral RNA clearance through the RNA interference process in Vero E6 cells or human lung microvascular endothelial cells. However, the use of siRNAs faces challenges due to their low biological stability and limited in vivo targeting ability. Despite their successful inhibition of Hantavirus replication in host cells, their antiviral efficacy may be hindered. In the current review, we focus on advances in therapeutic strategies, as antiviral medications, immune-base
Vandetanib is an anti-cancer drug called an antineoplastic kinase inhibitor. The FDA authorized vandetanib on April6, 2011 for the treatment of nonresectable, locally progressed, or metastatic medullary thyroid carcinoma in adults. Because Vandetanib can make the Q-T interval last longer, it shouldn't be given to people with serious heart problems like congenital long QT syndrome or heart failure that hasn't been fixed yet. This chapter provides an overview of Vandetanib's physical and molecular properties, mode of action, pharmacokinetics, and common applications. In furthermore, a detailed summary of the reported techniques of Vandetanib measurement will be provided to assist analysts in selecting the most practical approach for its estimation in routine analysis. This chapter will also explain the synthesis methods developed in the preparation of vandetanib as well as pharmacology of its. In addition, this section summarizes the analytical and characterization techniques utilized to characterize vandetanib row material.
Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC treatment modalities. However, recurrence or tumor metastasis remains the main challenge in the management of anaplastic thyroid cancer (ATC) and radioiodine (RAI) radioactive iodine-refractory differentiated thyroid cancer (RR-DTC). Several multi-tyrosine kinase inhibitors (MKIs), or immune checkpoint inhibitors in combination with MKIs, have emerged as novel therapies for controlling the progression of DTC, medullary thyroid cancer (MTC), and ATC. Here, we discuss and summarize the molecular basis of TC, review molecularly targeted therapeutic drugs in clinical research, and explore potentially novel molecular therapeutic targets. We focused on the evaluation of current and recently emerging tyrosine kinase inhibitors approved for systemic therapy for TC, including lenvatinib, sorafenib and cabozantinib in DTC, vandetanib, cabozantinib, and RET-specific inhibitor (selpercatinib and pralsetinib) in MTC, combination dabrafenib with trametinib in ATC. In addition, we also discuss promising treatments that are in clinical trials and may be incorporated into clinical practice in the future, briefly describe the resistance mechanisms of targeted therapies, emphasizing that personalized medicine is critical to the design of second-line therapies.
Physiological vascular endothelial cell division and angiogenesis occur during embryonic development, wound healing, in the endometrium during the menstrual cycle, and during placental development. Otherwise, vascular endothelial cells divide less than once per decade. Neoplasms are limited in size (∼ 1.0 mm) owing to a deficiency of oxygen and metabolic fuels. To grow larger, new blood vessels form from pre-existing vasculature by angiogenesis (capillary sprouting). During this process, mature endothelial cells replicate and become incorporated into new capillaries resulting in tumor growth. Angiogenesis results in part from the increased production of vascular endothelial growth factors (VEGFs). The human VEGF family consists of VEGF-A/B/C/D and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases (VEGFR1/2/3) and two nonprotein kinase receptors (neuropilin-1 and neuropilin-2). Semaphorins 3A-F/4A-G/5 A/B/6A-G/7 A are regulatory ligands that interact with their neuropilin and plexin receptors (PlxA1-A4/B1-B3/C1/D1) and regulate angiogenesis. Angiopoietin-1/2/4 interact with their Tie1/2 receptor protein-tyrosine kinases to modulate vasculogenesis and angiogenesis. Ephrin ligands (EfnA1/A2/A3/A4/A5/B1/B2/B3) and Ephrin receptors (EphA1/A2/A3/A4/A5/A6/A7/A8/A10/B1/B2/B3/B4/B6/) also contribute to angiogenesis. Platelet-derived growth factors, fibroblast growth factors, hepatocyte growth factor (c-Met), stem cell growth factor (Kit) receptor protein-tyrosine kinases, PKB/Akt, Src, and MAP kinases also participate in angiogenesis. Owing to its importance in tumor progression, the inhibition of angiogenic signaling represents an attractive cancer treatment. Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular
Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the