Περίληψη:
Introduction: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable. © 2020 The Author(s) Published by S. Karger AG, Basel.
Συγγραφείς:
Efstathiadou, Z.A.
Tsentidis, C.
Bargiota, A.
Daraki, V.
Kotsa, K.
Ntali, G.
Papanastasiou, L.
Tigas, S.
Toulis, K.
Pazaitou-Panayiotou, K.
Alevizaki, M.
Λέξεις-κλειδιά:
afatinib; aflibercept; alectinib; bevacizumab; cabozantinib; crizotinib; cyclophosphamide; doxorubicin; gefitinib; ibrutinib; imatinib; lapatinib; larotrectinib; nintedanib; orantinib; pazopanib; protein tyrosine kinase inhibitor; regorafenib; sorafenib; sunitinib; tipifarnib; vandetanib; vatalanib, abdominal pain; adult; advanced cancer; adverse drug reaction; anorexia; arthralgia; asthenia; cancer patient; cancer staging; cancer survival; clinical trial; constipation; controlled study; dysphonia; dyspnea; fatigue; headache; heart ventricle arrhythmia; human; hypertension; kidney disease; meta analysis; mucosa inflammation; musculoskeletal pain; myalgia; Newcastle-Ottawa scale; outcome assessment; perception deafness; peripheral edema; pregnancy outcome; progression free survival; quality control; retrospective study; Review; systematic review; thyroid cancer; thyroid medullary carcinoma; toxicity; treatment response time; vomiting
