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https://www.readbyqxmd.com/read/29783903/lenvatinib-and-its-use-in-the-treatment-of-unresectable-hepatocellular-carcinoma
#1
Mark A Baxter, Hilary Glen, Thomas Rj Evans
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for approximately 90% of cases. Patients often present at an advanced stage when treatment options are limited. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been the first-line treatment in this setting for almost a decade. Several subsequent targeted therapies have failed to demonstrate significant improvement in survival. The results of the REFLECT study suggest that lenvatinib, a multikinase inhibitor, may have promised as a first-line treatment in patients with advanced HCC...
May 22, 2018: Future Oncology
https://www.readbyqxmd.com/read/29783126/systemic-therapy-for-intermediate-and-advanced-hepatocellular-carcinoma-sorafenib-and-beyond
#2
REVIEW
Jean-Luc Raoul, Masatoshi Kudo, Richard S Finn, Julien Edeline, Maria Reig, Peter R Galle
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can be prevented...
May 17, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29779695/successful-treatment-switch-from-lenvatinib-to-sorafenib-in-a-patient-with-radioactive-iodine-refractory-differentiated-thyroid-cancer-intolerant-to-lenvatinib-due-to-severe-proteinuria
#3
Hideaki Goto, Naomi Kiyota, Naoki Otsuki, Yoshinori Imamura, Naoko Chayahara, Hirotaka Suto, Yoshiaki Nagatani, Masanori Toyoda, Toru Mukohara, Ken-Ichi Nibu, Toshihiko Kasahara, Yasuhiro Ito, Akihiro Miya, Mitsuyoshi Hirokawa, Akira Miyauchi, Hironobu Minami
Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib...
May 17, 2018: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/29769293/emerging-multitarget-tyrosine-kinase-inhibitors-in-the-treatment-of-neuroendocrine-neoplasms
#4
Federica Grillo, Tullio Florio, Francesco Ferraù, Elda Kara, Giuseppe Fanciulli, Antongiulio Faggiano, Annamaria A L Colao
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multi-target tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by regulatory agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in depth review on the studies published on the following MTKIs in neuroendocrine tumours: axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed...
May 16, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29752332/prolonged-duration-of-response-in-lenvatinib-responders-with-thyroid-cancer
#5
Andrew G Gianoukakis, Corina E Dutcus, Nicolas Batty, Matthew Guo, Mahadi Baig
We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS)...
June 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29737893/lenvatinib-for-the-treatment-of-kidney-cancer
#6
Hana Študentová, Denisa Vitásková, Bohuslav Melichar
Sequential administration of single targeted agents has evolved as the dominant paradigm in advanced RCC treatment. Lenvatinib plus everolimus is the first combination therapy in advanced RCC to show improvement in efficacy compared to monotherapy in advanced RCC while maintaining manageable toxicity profile. Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus...
June 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29733511/lenvatinib-inhibits-angiogenesis-and-tumor-fibroblast-growth-factor-signaling-pathways-in-human-hepatocellular-carcinoma-models
#7
Masahiro Matsuki, Taisuke Hoshi, Yuji Yamamoto, Megumi Ikemori-Kawada, Yukinori Minoshima, Yasuhiro Funahashi, Junji Matsui
Unresectable hepatocellular carcinoma (uHCC) is one of the most lethal and prevalent cancers worldwide, and current systemic therapeutic options for uHCC are limited. Lenvatinib, a multiple receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), recently demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority to sorafenib in a phase 3 study of uHCC. Here, we investigated mechanisms underlying the antitumor activity of lenvatinib in preclinical HCC models...
May 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29718721/lenvatinib-for-the-treatment-of-renal-cell-carcinoma
#8
Giandomenico Roviello, Silvia Paola Corona, Giovanni Bozza, Michele Aieta, Daniele Generali, Maria Grazia Rodriquenz, Anna Maria Mileo, Marco Imperatori, Anna Ianza, Raffaele Conca, Navid Sobhani
Renal cell carcinoma (RCC) accounts for 2-3% of all solid tumors. Expression of the receptor for the Vascular Endothelial Growth Factor (VEGF) is one of the most common features of RCC. Areas Covered: Lenvatinib is a novel multi-kinase inhibitor that has been studied in several solid tumors. It has shown promising results in the treatment of RCC, especially when combined with everolimus, In this review, we summarize the available data of lenvatinib for the treatment of advanced/metastatic renal cell carcinoma...
May 2, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29689631/novel-approaches-for-molecular-targeted-therapy-against-hepatocellular-carcinoma
#9
REVIEW
Yuji Eso, Hiroyuki Marusawa
Systemic chemotherapy using a multi-targeted tyrosine kinase inhibitor is an established treatment for advanced-stage tumors in various organs. Comprehensive genomic analyses using next-generation sequencing technology revealed the intra- and inter-tumor heterogeneity of human hepatocellular carcinomas (HCCs), and provided evidence for the use of therapeutic agents effective against multiple targets in tumor cells. Recently, the efficacy and safety of a multi-targeted tyrosine kinase inhibitor, lenvatinib, was confirmed by a randomized global phase III trial and thus lenvatinib was approved as first-line therapy for HCC, providing a new therapeutic option for patients in an advanced stage...
April 24, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29662829/lenvatinib-may-drastically-change-the-treatment-landscape-of-hepatocellular-carcinoma
#10
EDITORIAL
Masatoshi Kudo
No abstract text is available yet for this article.
March 2018: Liver Cancer
https://www.readbyqxmd.com/read/29662541/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-in-adults-following-prior-vascular-endothelial-growth-factor-targeted-therapy-clinical-trial-evidence-and-experience
#11
REVIEW
Susanne Osanto, Tom van der Hulle
Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits MET and AXL, both associated with poor prognosis in renal cell carcinoma (RCC), next to vascular endothelial growth factor receptor 2, KIT, FLT3 and RET. Chronic treatment with vascular endothelial growth factor receptor (VEGFR)-targeting sunitinib upregulates MET and AXL in RCC, indicating that cabozantinib may be particularly effective in patients with advanced RCC whose disease progressed on prior VEGFR-targeted treatment...
March 2018: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/29656442/treatment-emergent-hypertension-and-efficacy-in-the-phase-3-study-of-e7080-lenvatinib-in-differentiated-cancer-of-the-thyroid-select
#12
Lori J Wirth, Makoto Tahara, Bruce Robinson, Sanjeev Francis, Marcia S Brose, Mouhammed Amir Habra, Kate Newbold, Naomi Kiyota, Corina E Dutcus, Elton Mathias, Matthew Guo, Steven I Sherman, Martin Schlumberger
BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT)...
April 14, 2018: Cancer
https://www.readbyqxmd.com/read/29617171/lenvatinib-induced-renal-failure-two-first-time-case-reports-and-review-of-literature
#13
Stefano Cavalieri, Laura Cosmai, Augusto Genderini, Manuela Nebuloni, Antonella Tosoni, Federica Favales, Paola Pistillo, Cristiana Bergamini, Paolo Bossi, Lisa Licitra, Laura D Locati, Salvatore Alfieri
Lenvatinib (LEN) is a multi-kinase anti-angiogenic drug recently approved in several cancers. LEN is not easily manageable due to its complex safety profile. Proteinuria and renal failure (RF) were reported among the most frequent LEN-induced adverse events (AEs), often leading to discontinuations or dose modifications. Understanding the pathogenesis of these AEs could ameliorate the management of LEN-induced renal toxicity. Areas covered: We present two cases of LEN-induced renal failure (LIRF) with different pathogenesis...
April 4, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29615459/genetic-analysis-of-779-advanced-differentiated-and-anaplastic-thyroid-cancers
#14
Nikita Pozdeyev, Laurie Gay, Ethan S Sokol, Ryan J Hartmaier, Kelsi E Deaver, Stephanie N Davis, Jena D French, Pierre Vanden Borre, Daniel V LaBarbera, Aik-Choon Tan, Rebecca E Schweppe, Lauren Fishbein, Jeffrey S Ross, Bryan R Haugen, Daniel W Bowles
PURPOSE: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer and identify genetic alterations of potential diagnostic, prognostic and therapeutic significance. EXPERIMENTAL DESIGN: The genetic profiles of 583 advanced differentiated and 196 anaplastic thyroid cancers (ATC) generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed. RESULTS: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared to other thyroid cancer types...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29587324/-immunotherapy-for-renal-cell-carcinoma-current-status
#15
Marc-Oliver Grimm, Susan Foller
Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs...
April 2018: Aktuelle Urologie
https://www.readbyqxmd.com/read/29557694/lenvatinib-in-the-management-of-metastatic-renal-cell-carcinoma-a-promising-combination-therapy
#16
Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29547556/update-in-systemic-and-targeted-therapies-in-gastrointestinal-oncology
#17
Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29540641/management-of-anaplastic-thyroid-carcinoma-the-fruits-from-the-atc-research-consortium-of-japan
#18
Iwao Sugitani, Naoyoshi Onoda, Ken-Ichi Ito, Shinichi Suzuki
Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To obtain further insights into this "orphan disease," we have established the ATC Research Consortium of Japan (ATCCJ) in 2009. It represents a multicenter registry for ATC that have been treated in Japan. To date, 67 institutions have taken part in the collaborative research system and over 1,200 cases have been accumulated in its database. Using this big data, several retrospective studies were carried out to evaluate 1) prognostic factors to determine initial treatment policy, 2) significance of extended radical surgery for Stage IVB cases, 3) characteristics of ATC incidentally found on pathological examination and 4) pathological features of ATC with long-term survival...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29537878/number-needed-to-treat-in-indirect-treatment-comparison
#19
Patricia Guyot, Wei Cheng, Gabriel Tremblay, Ronda Copher, Heather Burnett, Xuan Li, Charles Makin
AIM: For dichotomous outcomes, odds ratio (OR) is one of the usual summary measures of indirect treatment comparison. A corresponding number needed to treat (NNT) estimate may facilitate understanding of the treatment effect. METHODS: We show how to estimate NNT based on OR results of a matching adjusted indirect comparison. We also have derived the explicit formula of its 95% CIs by applying the delta method, and as an alternative, a simulation-based method. RESULTS: The method was applied in a case study example in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients, comparing lenvatinib to sorafenib...
March 2018: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29517103/lenvatinib-exhibits-antineoplastic-activity-in-anaplastic-thyroid-cancer-in-vitro-and-in-vivo
#20
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
May 2018: Oncology Reports
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