scholarly journals Antiangiogenic tyrosine kinase inhibitors and immunotherapy as first-line treatment for metastatic renal cell carcinoma: is there an increased risk of hypothyroidism?

2021 ◽  
Vol 13 ◽  
pp. 175628722110297
Author(s):  
Giandomenico Roviello ◽  
Sebastiano Buti ◽  
Carlo Cattrini ◽  
Alessia Mennitto ◽  
Carlo Messina ◽  
...  
Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 321 ◽  
Author(s):  
Bernhard Ralla ◽  
Jonas Busch ◽  
Anne Flörcken ◽  
Jörg Westermann ◽  
Zhongwei Zhao ◽  
...  

Approximately 20–30% of patients with metastatic renal cell carcinoma (mRCC) in first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to primary resistance to this drug. At present, suitable robust biomarkers for prediction of a response are not available. Therefore, the aim of this study was to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs (sunitinib, n = 51; pazopanib, n = 6; sorafenib, n = 3) were categorized into responders and non-responders. Using the standard Response Evaluation Criteria in Solid Tumors, patients with progressive disease within 3 months after the start of treatment with TKI were considered as non-responders and those patients with stable disease and complete or partial response under the TKI treatment for at least 6 months as responders. Based on a miRNA microarray expression profile in the two stratified groups of patients, seven differentially expressed miRNAs were validated using droplet digital reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) assays in the two groups. Receiver operating characteristic curve analysis and binary logistic regression of response prediction were performed. MiR-9-5p and miR-489-3p were able to discriminate between the two groups. MiR-9-5p, as the most significant miRNA, improved the correct prediction of primary resistance against TKIs in comparison to that of conventional clinicopathological variables. The results of the decision curve analyses, Kaplan-Meier analyses and Cox regression analyses confirmed the potential of miR-9-5p in the prediction of response to TKIs and the prediction of progression-free survival after the initiation of TKI treatment.


2013 ◽  
Vol 3 (4) ◽  
pp. 281 ◽  
Author(s):  
Mark Warren ◽  
Peter M. Venner ◽  
Scott North ◽  
Tina Cheng ◽  
Chris Venner ◽  
...  

Background: We performed a retrospective population-based studyto assess the impact of tyrosine kinase inhibitors (TKIs) on overallsurvival (OS) in patients treated for metastatic renal cell carcinoma(mRCC) in Alberta, Canada and to assess the impact of nephrectomyon OS in patients treated with TKIs.Methods: We identified 134 patients who began taking a TKIbetween December 2003 and June 2007 for mRCC in Alberta. Wecompared survival in this group to that in an earlier cohort of141 pa tients treated with interferon-α (IFN-α) between May 1995and March 2003. We used the Kaplan–Meier method to determineOS, and we used a Cox proportional hazards model to determinehazard ratios (HRs) and confidence intervals (CIs). We performedmultivariate analysis to assess the impact of neprhectomy on OS.Results: Of the 134 patients treated with TKIs, 81 received treatmentin the first-line setting, whereas 53 received treatment after priorIFN-α therapy. All 141 patients from the IFN-α cohort receivedtreatment in the first-line setting. Patients treated with TKIs had animproved OS compared with the IFN-α cohort (HR 0.61, 95% CI0.45–0.83, p = 0.001). The median OS was 18 months in the TKIgroup and 10 months in the IFN-α group. The benefit of TKIs wasconfined to favourable and intermediate risk groups according tothe Memorial Sloan-Kettering Cancer Center prognostic model.Prior nephrectomy was associated with improved OS in the TKIcohort, independent of other prognostic factors.Conclusion: Tyrosine kinase inhibitors improve OS compared withIFN-α in mRCC. In patients treated with TKIs, prior nephrectomyis associated with improved survival independent of other prognosticvariables.Contexte : Une étude rétrospective de population a été menée afind’évaluer l’effet des inhibiteurs de la tyrosine-kinase (ITK) sur lasurvie globale (SG) des patients atteints d’un néphrocarcinomemétastatique et d’évaluer l’impact d’une néphrectomie sur la SGdes patients traités par ITK.Méthodes : Cent trente-quatre patients en Alberta ont entrepris untraitement par ITK entre decembre 2003 et juin 2007 en raisond’un néphrocarcinome. On a comparé les taux de survie dans cegroupe avec ceux d’un groupe de 141 patients ayant entrepris untraitement de première intention par IFN-α entre mai 1995 et mars2003. La survie globale a été calculée à l’aide de la méthode deKaplan Meier, et le risque relatif (RR) et les intervalles de confiance(IC) ont été calculés à l’aide du modèle des risques proportionnelsde Cox. Une analyse multivariée a permis d’évaluer l’impact dela néphrectomie sur la SG dans la population globale de l’étuded’une part et chez les patients traités par ITK d’autre part.Résultats : Les 134 patients ayant entrepris un traitement par ITK ontété répartis ainsi : traitement de première intention, 81 patients, ettraitement de seconde intention après un traitement par IFN-α,53 patients. Les patients traités par ITK ont montré une SG supérieurepar rapport aux patients traités par IFN-α (RR 0,61, IC à 95 % 0,45–0,83, p = 0,001). La SG médiane était de 18 mois chez les patientstraités par ITK et de 10 mois chez les patients traités par IFN-α. Letraitement par ITK n’a eu un avantage que chez les patients atteintsde néphrocarcinome métastatique présentant un risque faible ouintermédiaire selon le modèle du Memorial Sloan-Kettering CancerCener. Une néphrectomie antérieure a été associée à une meilleureSG dans la cohorte traitée par ITK, indépendamment des autres facteurspronostics.Conclusion : Le traitement par ITK a amélioré la SG par rapport autraitement par IFN-α dans une population « réelle ». Une néphrectomieantérieure a été associée à une SG supérieure chez lespatients traités par ITK.


2019 ◽  
Vol 15 (22) ◽  
pp. 2657-2666
Author(s):  
Giuseppe Procopio ◽  
Sandro Pignata ◽  
Amelia Altavilla ◽  
Laura Attademo ◽  
Delia De Lisi ◽  
...  

Tyrosine kinase inhibitors still play a very important role in the treatment of metastatic renal cell carcinoma despite a continuously changing scenario, in which immunotherapy and several combination-based approaches are also available. In this light, patient-reported outcomes and health-related quality of life are important factors in the selection of the best first-line treatment. This Review focuses on the existing evidence on patient-reported outcomes and health-related quality of life with several tyrosine kinase inhibitors (pazopanib, sunitinib, cabozantinib and tivozanib) used as first-line treatment for metastatic renal cell carcinoma.


2019 ◽  
Vol 15 (9) ◽  
pp. 925-927
Author(s):  
Samet Yaman ◽  
Burak Bilgin ◽  
Mehmet AN Şendur ◽  
Mutlu Hızal ◽  
Muhammed Bülent Akıncı ◽  
...  

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