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Cabozantinib

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https://www.readbyqxmd.com/read/29146618/management-of-adverse-events-associated-with-cabozantinib-therapy-in-renal-cell-carcinoma
#1
REVIEW
Manuela Schmidinger, Romano Danesi
Cabozantinib was recently approved for the treatment of advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Cabozantinib is a multikinase inhibitor targeting VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. A 60-mg daily dose led to improved overall survival and progression-free survival (PFS) versus everolimus in advanced RCC patients as a second- or later-line treatment in the METEOR trial...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29134564/seom-clinical-guideline-for-treatment-of-kidney-cancer-2017
#2
E Gallardo, M J Méndez-Vidal, J L Pérez-Gracia, J M Sepúlveda-Sánchez, M Campayo, I Chirivella-González, X García-Del-Muro, A González-Del-Alba, E Grande, C Suárez
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma...
November 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29128427/osimertinib-and-cabozantinib-combinatorial-therapy-in-an-egfr-mutant-lung-adenocarcinoma-patient-with-multiple-met-secondary-site-mutations-after-resistance-to-crizotinib
#3
Jin Kang, Hua-Jun Chen, Zheng Wang, Jing Liu, Bing Li, Tengfei Zhang, Zhenfan Yang, Yi-Long Wu, Jin-Ji Yang
No abstract text is available yet for this article.
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29089775/practical-management-of-adverse-events-associated-with-cabozantinib-treatment-in-patients-with-renal-cell-carcinoma
#4
REVIEW
Benjamin S Gerendash, Patricia A Creel
Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus. Adverse events (AEs) were common for patients receiving cabozantinib, but were effectively managed with supportive care and dose modifications, as discontinuations of cabozantinib due to an AE were infrequent...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29082855/comparative-efficacy-and-safety-of-second-line-treatments-for-advanced-non-small-cell-lung-cancer-with-wild-type-or-unknown-status-for-epidermal-growth-factor-receptor-a-systematic-review-and-network-meta-analysis
#5
Perrine Créquit, Anna Chaimani, Amélie Yavchitz, Nassima Attiche, Jacques Cadranel, Ludovic Trinquart, Philippe Ravaud
BACKGROUND: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis...
October 30, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29074560/a-network-meta-analysis-of-short-term-efficacy-of-different-single-drug-targeted-therapies-in-the-treatment-of-renal-cell-carcinoma
#6
Hong-Ling He, Wan-Xia Yao
The network meta-analysis was conducted to compare the short-term efficacy of different single-drug targeted therapies in the treatment of renal cell carcinoma (RCC). We initially searched databases for randomized controlled trials (RCTs) on different single-drug targeted therapies in treating RCC. The meta-analysis combined the direct and indirect evidence to calculate the pooled odds ratios (OR) and draw surface under the cumulative ranking curves (SUCRA). A total of 14 eligible RCTs were ultimately selected...
October 26, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#7
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Dis Transl Med
https://www.readbyqxmd.com/read/29061793/the-anti-tumor-effect-of-cabozantinib-on-ovarian-clear-cell-carcinoma-in-vitro-and-in-vivo
#8
Makiko Nakatani, Hidemichi Watari, Takashi Mitamura, Lei Wang, Yutaka Hatanaka, Kanako C Hatanaka, Kohei Honda, Toshiyuki Nomura, Hiroshi Nishihara, Shinya Tanaka, Noriaki Sakuragi
BACKGROUND: Several reports have shown that the overexpression of the MET proto-oncogene, receptor tyrosine kinase (MET), was more frequently observed in clear cell carcinoma (CCC) than in non-CCC. We evaluated the antitumor activity of cabozantinib, that targets MET. MATERIALS AND METHODS: A gene expression analysis of tumors from human ovarian cancers was carried out by transcriptome sequencing. An in vitro 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay (MTT assay) and in vivo experiments were performed to determine the activity of cabozantinib...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29059635/phase-ii-randomised-discontinuation-trial-of-cabozantinib-in-patients-with-advanced-solid-tumours
#9
Patrick Schöffski, Michael Gordon, David C Smith, Razelle Kurzrock, Adil Daud, Nicholas J Vogelzang, Yihua Lee, Christian Scheffold, Geoffrey I Shapiro
BACKGROUND: Cabozantinib is an inhibitor of tyrosine kinases, including MET, vascular endothelial growth factor receptor, AXL and RET. This multi-cohort phase II randomised discontinuation trial explored anticancer activity of cabozantinib in nine tumour types. PATIENTS AND METHODS: Cabozantinib was administered (100 mg, once daily) to patients with advanced, recurrent or metastatic cancers. Those with stable disease at week 12 were randomised 1:1 to cabozantinib or placebo...
October 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29057215/targeted-therapy-for-medullary-thyroid-cancer-a-review
#10
REVIEW
S R Priya, Chandra Shekhar Dravid, Raghunadharao Digumarti, Mitali Dandekar
Medullary thyroid cancers (MTCs) constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29045520/overall-survival-analysis-of-exam-a-phase-iii-trial-of-cabozantinib-in-patients-with-radiographically-progressive-medullary-thyroid-carcinoma
#11
M Schlumberger, R Elisei, S Müller, P Schöffski, M Brose, M Shah, L Licitra, J Krajewska, M C Kreissl, B Niederle, E E W Cohen, L Wirth, H Ali, D O Clary, Y Yaron, M Mangeshkar, D Ball, B Nelkin, S Sherman
Background: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. Patients and methods: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045250/clinical-decision-making-for-immunotherapy-in-metastatic-renal-cell-carcinoma
#12
Manuela Schmidinger
PURPOSE OF REVIEW: To review the treatment options in metastatic renal cell carcinoma (mRCC) in the light of new immunotherapy results. RECENT FINDINGS: Second-line treatment strategies for treatment of mRCC after progression on first-line VEGF-targeted therapy have recently undergone a major change. Treatment guidelines currently recommend the use of either nivolumab, a programmed cell death 1 (PD-1) inhibitor, or cabozantinib, an inhibitor of multiple receptor tyrosine kinases, as preferred choices...
October 17, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29036345/phase-ii-study-of-cabozantinib-in-patients-with-progressive-glioblastoma-subset-analysis-of-patients-with-prior-antiangiogenic-therapy
#13
Timothy F Cloughesy, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jerry Ping, Jaymes Holland, Ron Weitzman, Patrick Y Wen
Background: Cabozantinib is a potent, multi-target inhibitor of hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor-2 (VEGFR2). This open-label, phase II trial evaluated cabozantinib in patients with recurrent or progressive glioblastoma (GBM; NCT00704288). Methods: Patients were initially enrolled to a starting cabozantinib dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of safety concerns. Treatment continued until disease progression or unacceptable toxicity...
October 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#14
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29033542/axitinib-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#15
REVIEW
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard
Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC) patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29028513/occurrence-and-significance-of-morphologic-changes-in-patients-with-metastatic-triple-negative-breast-cancer-treated-with-cabozantinib
#16
Atul B Shinagare, Bhanusupriya Somarouthu, Hao Guo, Sara M Tolaney, Nikhil H Ramaiya
OBJECTIVE: To compare performance of RECIST1.1 and Choi criteria in assessment of patients with metastatic triple-negative breast cancer treated with cabozantinib. METHODS: Thirty patients with metastatic triple-negative breast cancer enrolled in phase 2 clinical trial received cabozantinib. Clinical benefit rates assessed by prospectively determined RECIST1.1 and retrospectively assessed Choi criteria were compared. RESULTS: Decreased tumor density (≥15%) at first follow-up was seen in 22/30(73%) patients...
September 28, 2017: Clinical Imaging
https://www.readbyqxmd.com/read/29016998/phase-ii-study-of-cabozantinib-in-patients-with-progressive-glioblastoma-subset-analysis-of-patients-naive-to-antiangiogenic-therapy
#17
Patrick Y Wen, Jan Drappatz, John de Groot, Michael D Prados, David A Reardon, David Schiff, Marc Chamberlain, Tom Mikkelsen, Annick Desjardins, Jaymes Holland, Jerry Ping, Ron Weitzman, Timothy F Cloughesy
Background: Cabozantinib is a tyrosine kinase inhibitor with activity against VEGFR2 and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM; NCT00704288). Methods: Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity...
August 14, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28994424/thyroid-cancer-cabozantinib-effective-in-selected-patients
#18
Peter Sidaway
No abstract text is available yet for this article.
December 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28974985/cabozantinib-in-metastatic-renal-cell-carcinoma-latest-findings-and-clinical-potential
#19
REVIEW
Melissa Bersanelli, Sebastiano Buti
Since the advent of immunotherapy revolutionized the treatment of metastatic renal cell carcinoma (mRCC), the attention of oncologists has been unavoidably shifted from tyrosine kinase inhibitors (TKIs) to immune checkpoint blockade, with the associated risk of listing cabozantinib as just one of many available TKIs. On the contrary, we think that cabozantinib represents a very good option for mRCC treatment, with outstanding outcomes in terms of response rate, progression-free survival, overall survival and quick time to treatment response...
October 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28960265/cabozantinib-is-well-tolerated-in-acute-myeloid-leukemia-and-effectively-inhibits-the-resistance-conferring-flt3-tyrosine-kinase-domain-f691-mutation
#20
Amir T Fathi, Traci M Blonquist, Daniela Hernandez, Philip C Amrein, Karen K Ballen, Malgorzata McMasters, David E Avigan, Robin Joyce, Emma K Logan, Gabriela Hobbs, Andrew M Brunner, Christelle Joseph, Ashley M Perry, Meghan Burke, Tanya Behnan, Julia Foster, Meghan K Bergeron, Jenna A Moran, Aura Y Ramos, Tina T Som, Jessica Rae, Kaitlyn M Fishman, Kristin L McGregor, Christine Connolly, Donna S Neuberg, Mark J Levis
BACKGROUND: Cabozantinib, a tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 (FLT3), MET, AXL, vascular endothelial growth factor receptor, and KIT, is approved for use in multiple malignancies. We assessed the safety and tolerability of cabozantinib in AML, given up-regulation of multiple relevant pathways. METHODS: Adults were eligible if they were 18 years old or older with relapsed/refractory AML or if they were 70 years old or older with newly diagnosed AML but were ineligible for conventional therapy...
September 28, 2017: Cancer
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