التفاصيل البيبلوغرافية
| العنوان: |
Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma: Response monitoring and resistance prediction with positron emission tomography and tumor characteristics (REPOSIT): Study protocol of a phase II, open-label, multicenter study |
| المؤلفون: |
van der Hiel, Bernies, Haanen, John B A G, Stokkel, Marcel P M, Peeper, Daniel S., Jimenez, Connie R., Beijnen, Jos H, van de Wiel, Bart A., Boellaard, Ronald, van den Eertwegh, Alfons J M, van Tinteren, H., Wessels, Lodewyk F A, Lolkema, Martijn P J K, Hoekstra, Otto S, Hospers, Geke A P, Brouwers, Adrienne H, Koornstra, R.H.T., Arens, A. I. J., de Vos, F. Y.F.L., Hobbelink, M. G.G., Kapiteijn, H. W., de Geus-Oei, L. F., Kruit, W. H.J., Verzijlbergen, F.J., Aarts, M. J.B., Mottaghy, F. M., de Groot, J. W.B., Knollema, S., Piersma, D., Agool, A., Vreugdenhil, Art, Liem, I H, van den Berkmortel, Franchette W P J, Schreurs, M.W., REPOSIT study group |
| المساهمون: |
MS Medische Oncologie, Cancer, UMC Utrecht, Arts-assistenten Nucleaire Geneesk. |
| سنة النشر: |
2017 |
| مصطلحات موضوعية: |
F-FDG, F-FLT, BRAF inhibitor, MEK inhibitor, PET/CT, Resistance, Stage IIIc/IV melanoma, Sulfonamides/administration & dosage, Melanoma/diagnostic imaging, Azetidines/administration & dosage, Piperidines/administration & dosage, Skin Neoplasms/diagnostic imaging, Humans, Drug Resistance, Neoplasm, Treatment Outcome, Positron-Emission Tomography, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Indoles/administration & dosage, Disease-Free Survival, Vemurafenib, Multicenter Studies as Topic, Neoplasm Staging, Research Design, Clinical Trials, Phase II as Topic, Genetics, Oncology, Cancer Research, Journal Article |
| الوصف: |
Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. Discussion: The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
image/pdf |
| اللغة: |
English |
| تدمد: |
1471-2407 |
| العلاقة: |
https://dspace.library.uu.nl/handle/1874/356417Test |
| الإتاحة: |
https://dspace.library.uu.nl/handle/1874/356417Test |
| حقوق: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.49B18048 |
| قاعدة البيانات: |
BASE |
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