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Anikó Maráz, Adrienn Cserháti, Gabriella Uhercsák, Éva Szilágyi, Zoltán Varga, János Révész, Renáta Kószó, Linda Varga, Zsuzsanna Kahán
BACKGROUND: In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. METHODS: From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62...
March 15, 2018: BMC Cancer
Hiroto Matsuda, Satoshi Tamada, Minoru Kato, Akira Yamamoto, Taro Iguchi, Tatsuya Nakatani
A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared...
March 2018: Urology Case Reports
Michael Nagel, Julia Schulz, Annett Maderer, Katrin Goepfert, Nadine Gehrke, Thomas Thomaidis, Peter C Thuss-Patience, Salah E Al-Batran, Susanna Hegewisch-Becker, Peter Grimminger, Peter Robert Galle, Markus Möhler, Jörn Markus Schattenberg
BACKGROUND: Gastric cancer is common malignancy and exhibits a poor prognosis. At the time of diagnosis, the majority of patients present with metastatic disease which precludes curative treatment. Non-invasive biomarkers which discriminate early from advanced stages or predict the response to treatment are urgently required. This study explored the cytokeratin-18 fragment M30 and full-length cytokeratin-18 M65 in predicting treatment response and survival in a randomized, placebo-controlled trial of advanced gastric cancer...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects...
April 2018: International Journal of Oncology
Maudy Walraven, Marjolein Y V Homs, Astrid A M van der Veldt, Henk Dekker, Jose Koldenhof, Richard Honeywell, Arjan Barendrecht, Silvie A E Sebastian, Naomi Parr, Arnold C Koekman, Emile E Voest, Mark Roest, Suzanne J A Korporaal, Henk M W Verheul
INTRODUCTION: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings...
March 12, 2018: Angiogenesis
Toni K Choueiri, James Larkin, Mototsugu Oya, Fiona Thistlethwaite, Marcella Martignoni, Paul Nathan, Thomas Powles, David McDermott, Paul B Robbins, David D Chism, Daniel Cho, Michael B Atkins, Michael S Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Camilla Fowst, Alessandra di Pietro, Brian I Rini
BACKGROUND: The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma...
March 9, 2018: Lancet Oncology
G Lendínez-Cano, I Osman García, C B Congregado Ruiz, J M Conde Sánchez, R A Medina López
OBJECTIVES: To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. MATERIAL AND METHODS: We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves...
March 7, 2018: Actas Urologicas Españolas
Bishal Gyawali, Daniel A Goldstein
No abstract text is available yet for this article.
March 8, 2018: JAMA Oncology
Anna Pellat, Chantal Dreyer, Camille Couffignal, Thomas Walter, Catherine Lombard-Bohas, Patricia Niccoli, Jean François Seitz, Olivia Hentic, Thierry André, Romain Coriat, Sandrine Faivre, Magaly Zappa, Philippe Ruszniewski, Nicolas Pote, Anne Couvelard, Eric Raymond
BACKGROUND/AIMS: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumours (PanNET) where sunitinib was shown to prolong progression-free survival, leading to nationwide approval. However, clinical experience in patients with grade 3 gastroenteropancreatic neuroendocrine neoplasms (GEPNEN-G3) remains limited. This prospective phase II trial evaluated potential predictive biomarkers of sunitinib activity in patients with advanced GEPNEN-G3. METHODS: Sunitinib was given at a dose of 37...
March 8, 2018: Neuroendocrinology
Toshirou Fukushima, Daisuke Gomi, Noriko Seno, Takahiko Gibo, Takashi Kobayashi, Nodoka Sekiguchi, Hirohide Matsushita, Yoshiko Kasahara, Keiko Mamiya, Tomonobu Koizumi
Pulmonary neuroendocrine tumors are rare, and there have been very few reports regarding optimal chemotherapeutic regimens. Two molecular targeted agents, everolimus and sunitinib, have recently been shown to provide an additional treatment benefit for pulmonary neuroendocrine tumors. However, little information is available regarding the usefulness of streptozocin chemotherapy. Here, we encountered a case of relapsed and refractory mediastinal atypical carcinoid tumor associated with multiple endocrine neoplasia type 1 for various cytotoxic and molecular targeted agents...
January 2018: Case Reports in Oncology
Tarik Mahfoud, Rachid Tanz, Mohamed Réda Khmamouche, Mohamed Allaoui, Rhizlane Belbaraka, Mouna Khouchani, Mohamed Ichou
Synchronous primary cancers involving the pancreas and kidney are extremely rare and poorly documented. We report the first case of this association treated with chemotherapy and tyrosine kinase inhibitor. A 70-year-old woman presented with a 2-month history of epigastric pain with weight loss of 12 kg. Two weeks previously, she had presented with jaundice and pelvic pain. A computed tomography (CT) scan of the body revealed the presence of an irregular mass in the body of the pancreas, encasing the celiac trunk, with dilatation of the biliary tract...
September 2017: Case Reports in Oncology
Peter Makhov, Sei Naito, Miki Haifler, Alexander Kutikov, Yanis Boumber, Robert G Uzzo, Vladimir M Kolenko
Renal cell carcinoma (RCC) is the most common form of kidney cancer. While cure remains exceptionally infrequent in RCC patients with systemic or recurrent disease, current targeted molecular strategies, including multi-targeted tyrosine kinase inhibitors (TKIs), notably changed the treatment paradigm of advanced renal cancer. Yet, complete and durable responses have been noted in only a few cases. Our studies reveal that sunitinib triggers two resistance-promoting signaling pathways in RCC cells, which emanate from the endoplasmic reticulum (ER) stress response: a PERK-driven ER stress response that induces expression of the pro-tumorigenic cytokines IL-6, IL-8, and TNF-α, and a TRAF2-mediated NF-κB survival program that protects tumor cells against cell death...
March 7, 2018: Cell Death & Disease
Kenji Nakano, Shunji Takahashi
Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib's approval as a treatment for gastrointestinal stromal tumors (GISTs) has been a great achievement...
March 5, 2018: International Journal of Molecular Sciences
Elaine Silveira, Isadora Pontes Cavalcante, Jean Lucas Kremer, Pedro Omori Ribeiro de Mendonça, Claudimara Ferini Pacicco Lotfi
Background: New drugs for adrenocortical carcinoma (ACC) are needed because most patients undergo rapid disease progression despite surgery and adjuvant therapy with mitotane. In this study, we aimed to investigate the in vitro effects of different chemotherapy drugs, alone or combined with mitotane, on the viability of adrenocortical carcinoma cells. Methods: Everolimus, sunitinib, zoledronic acid, imatinib and nilotinib cytotoxicity, alone or combined with mitotane were tested on ACC H295R cells in monolayer or spheroid cultures using MTS assays and confocal microscopy...
2018: Cancer Cell International
Donatienne Van Weehaeghe, Olivier Gheysens, Vincent Vandecaveye, Patrick Schöffski, Koen Van Laere, Christophe M Deroose
BACKGROUND: Gastro-intestinal stromal tumors (GISTs) are very rare tumors of the gastro-intestinal tract, originating from the interstitial cells of Cajal or a common cell precursor which both express type III tyrosine kinase receptors. Regorafenib is an oral multi-kinase inhibitor used to treat gastro-intestinal stromal tumors. To our knowledge this is the first case in literature to show the response of regorafenib on PET. CASE PRESENTATION: A 37-year-old male with lower abdominal pain and weight loss was referred to our hospital...
March 5, 2018: BMC Cancer
Elvira Schmidt, Johanna Lister, Monika Neumann, Witold Wiecek, Shuai Fu, Anne-Lise Vataire, Jelena Sostar, Shengnan Huang, Florence Marteau
BACKGROUND: Cabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC). OBJECTIVE: To indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC. METHODS: We conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS)...
February 28, 2018: Targeted Oncology
Masami Miki, Ken Kawabe, Hisato Igarashi, Tatsuro Abe, Yoshihiro Ohishi, Risa Hashimoto, Takashi Karashima, Ichiro Yamasaki, Keiji Inoue, Tetsuhide Ito, Yoshihiro Ogawa
A 45-year old woman who underwent several surgeries for tumors associated with von Hippel Lindau disease (VHL) was referred to our hospital due to a pancreatic tumor and liver tumors. She was diagnosed with pancreatic neuroendocrine tumor (NET) with a Ki67 index of 40% based on the examination of a biopsy specimen of the liver tumors. She was treated with everolimus for 6 months and sunitinib for 6 weeks as first- and second-line therapies. She survived for 13 months. At autopsy the diagnosis of pancreatic neuroendocrine tumor (NET)-G3 was confirmed...
February 28, 2018: Internal Medicine
Xiaoyan Liu, Jesse J Swen, Meta H M Diekstra, Epie Boven, Daniel Castellano, Hans Gelderblom, Ron Hj Mathijssen, Sita H Vermeulen, Egbert Oosterwijk, Kerstin Junker, Max Roessler, Kristin Alexiusdottir, Asgerdur Sverrisdottir, Marius T Radu, Valentin Ambert, Timothy Eisen, Anne Y Warren, Cristina Rodríguez-Antona, Jesus García-Donás, Karel K M Koudijs, Stefan Böhringer, Lambertus A Kiemeney, Brian Rini, Henk-Jan Guchelaar
PURPOSE: The survival of patients with clear cell metastatic renal cell carcinoma (cc-mRCC) has improved substantially since the introduction of tyrosine kinase inhibitors (TKIs). With the fact that TKIs interact with immune responses, we investigated whether polymorphisms of genes involved in immune checkpoints are related to the clinical outcome of cc-mRCC patients treated with sunitinib as first TKI. EXPERIMENTAL DESIGN: 27 single nucleotide polymorphisms (SNPs) in CD274 (PD-L1) , PDCD1 (PD-1) and CTLA-4 were tested for a possible association with progression-free survival (PFS) and overall survival (OS) in a discovery cohort of 550 sunitinib-treated cc-mRCC patients...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ilaria Marech, Michele Ammendola, Christian Leporini, Rosa Patruno, Maria Luposella, Nicola Zizzo, Giuseppe Passantino, Rosario Sacco, Ammad Ahmad Farooqi, Valeria Zuccalà, Silvana Leo, Rosalba Dentamaro, Mariangela Porcelli, Pietro Gadaleta, Giovambattista De Sarro, Cosmo Damiano Gadaleta, Girolamo Ranieri
C-Kit protein is a transmembrane tyrosine kinase (TK) receptor (c-KitR-TK), which is predominantly expressed on mast cells (MCs) playing a role in tumor angiogenesis. It could be also expressed on epithelial breast cancer cells (EBCCs), but no data have been published regarding the correlation between mast cells positive to c-KitR (MCs-c-KitR), EBCCs positive to c-KitR (EBCCs-c-KitR), BC angiogenesis in terms of microvessel density (MVD) and the main clinic-pathological features. This study aims to evaluate the above parameters and their correlations in a series of selected 121 female early BC patients...
January 30, 2018: Oncotarget
Gloria Golinelli, Andrea Toso, Maria Silvia Rosa, Paolo Aluffi Valletti, Francesco Pia
Skull base metastases are extremely rare. The authors report a case of a 65-year-old man who presented with a headache and diplopia secondary to a skull base metastasis from occult renal cell carcinoma. Since there were no other systemic metastases, radical nephrectomy and radiotherapy of the unresectable skull base location were performed. He subsequently received immunotherapy with sunitinib, everolimus, and sorafenib with local and systemic control of the disease after 53 months from surgery. When metastasis is unresectable radical nephrectomy and radiotherapy aimed at the metastasis may be of benefit improving quality of life...
February 26, 2018: Journal of Craniofacial Surgery
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