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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
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
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
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
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...
March 8, 2018: Oncology Reports
Reiko Kimura-Tsuchiya, Eisaku Sasaki, Izumi Nakamura, Satoshi Suzuki, Satoshi Kawana, Chiyo Okouchi, Toshihiko Fukushima, Yuko Hashimoto, Shinichi Suzuki, Shigehira Saji
Lenvatinib is an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, as well as platelet-derived growth factor receptor α, RET, and KIT. At present, lenvatinib is used in the treatment of thyroid cancer and renal cell carcinoma. We herein report a case of a 67-year-old patient with squamous cell carcinoma of unknown primary who was effectively treated with lenvatinib. The patient was initially diagnosed as having undifferentiated thyroid cancer, and after total thyroidectomy and bilateral lymph node dissection, lenvatinib was administered for the treatment of residual lymph node metastasis...
January 2018: Case Reports in Oncology
Jean-Charles Nault, Peter R Galle, Jens U Marquardt
Hepatocellular carcinomas (HCC) are characterized by considerable phenotypic and molecular heterogeneity. Treatment and design of clinical trials are particularly challenging due a co-existing liver disease present in the majority of patients which limits aggressive therapeutic options. Despite positive results in recent phase III clinical trials, that confirmed the high value of antiangiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities, failure of several large randomized controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of findings from translational studies to overcome this unmet clinical need...
March 2, 2018: Journal of Hepatology
Alice Nervo, Marco Gallo, Maria Teresa Samà, Francesco Felicetti, Martina Alfano, Enrica Migliore, Filippo Marchisio, Rita Berardelli, Emanuela Arvat, Alessandro Piovesan
BACKGROUND: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice. PATIENTS AND METHODS: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed. RESULTS: After a median follow-up of 13...
March 2018: Anticancer Research
Hugh Thomas
No abstract text is available yet for this article.
February 28, 2018: Nature Reviews. Gastroenterology & Hepatology
Nizar M Tannir, Sumanta K Pal, Michael B Atkins
The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small-molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin...
February 27, 2018: Oncologist
Silvia Martina Ferrari, Ilaria Ruffilli, Marco Centanni, Camilla Virili, Gabriele Materazzi, Magdalini Alexopoulou, Mario Miccoli, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), platelet-derived growth factor receptor (PDGFR)α, rearranged during transfection (RET), and v-kit (KIT) signaling networks implicated in tumor angiogenesis. METHOD: Here we review the scientific literature about lenvatinib in the treatment of thyroid cancer...
February 19, 2018: Recent Patents on Anti-cancer Drug Discovery
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
Masatoshi Kudo, Richard S Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean Frederic Blanc, Arndt Vogel, Dmitry Komov, T R Jeffry Evans, Carlos Lopez, Corina Dutcus, Matthew Guo, Kenichi Saito, Silvija Kraljevic, Toshiyuki Tamai, Min Ren, Ann-Lii Cheng
BACKGROUND: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. METHODS: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions...
February 9, 2018: Lancet
María Reig, Jordi Bruix
No abstract text is available yet for this article.
February 9, 2018: Lancet
Takashi Nishi, Akiko Igawa, Akimasa Nishimura, Kenichi Hakamada
We report a case of a rupture of the common carotid artery caused by the medication of lenvatinib. The patient, 70-yearold female, was referred to our hospital by unresectable papillary thyroid cancer infiltrated the left common carotid artery. Externalbeam radiotherapy and radioiodine therapy were undergone after totalthyroidectomy. After 1 year 7 months from operation, she admitted our hospital due to left shoulder pain and dysphagia caused by the growing left cervical tumor. The medication of lenvatinib was decided after the careful informed consent...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Koichi Suyama, Mai Tomiguchi, Takashi Takeshita, Aiko Sueta, Mutsuko Yamamoto-Ibusuki, Mototsugu Shimokawa, Yutaka Yamamoto, Hirotaka Iwase
Lenvatinib, a multi-tyrosine kinase inhibitor, has been proven to be an effective treatment option for patients with iodine-131-refractory thyroid cancer. Many adverse effects of lenvatinib have been reported; thus, dose reduction is common. However, a few studies have analyzed the causes of lenvatinib dose reduction in daily clinical practice. Here, we investigate the factors involved in early lenvatinib dose reduction to analyze lenvatinib dose modification. We analyzed 20 thyroid cancer patients who began receiving lenvatinib at the Kumamoto University Hospital Cancer Center from July 2015 to November 2016...
January 31, 2018: Medical Oncology
Sedighe Sadeghian-Rizi, Ghadamali Khodarahmi, Amirhossein Sakhteman, Ali Jahanian-Najafabadi, Mahboubeh Rostami, Mahmoud Mirzaei, Farshid Hassanzadeh
Diaryl urea derivatives have exhibited a broad spectrum of biochemical effects and pharmaceutical applications. Several diaryl urea derivatives such as sorafenib, regorafenib, linifanib, and tivozanib and lenvatinib are in clinical trial or clinical use. Therefore, development of small molecules within the diaryl urea scaffold with the ability of binding to variety of enzymes and receptors in the biological system are an interesting topic for researchers. Sorafenib as a diaryl urea derivative is a well-known anticancer agent...
February 2018: Research in Pharmaceutical Sciences
(no author information available yet)
No abstract text is available yet for this article.
December 2017: Australian Prescriber
Catharina Balmelli, Nikola Railic, Marco Siano, Kristin Feuerlein, Richard Cathomas, Valerie Cristina, Christiane Güthner, Stefan Zimmermann, Sabine Weidner, Miklos Pless, Frank Stenner, Sacha I Rothschild
Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval...
2018: Journal of Cancer
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