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Adjuvant sunitinib

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https://read.qxmd.com/read/30975543/unmasking-a-new-prognostic-marker-and-therapeutic-target-from-the-gdnf-ret-pit1-p14arf-p53-pathway-in-acromegaly
#1
Miguel Chenlo, Iria A Rodriguez-Gomez, Ramon Serramito, Angela R Garcia-Rendueles, Rocío Villar-Taibo, Eva Fernandez-Rodriguez, Sihara Perez-Romero, Maria Suarez-Fariña, Alfredo Garcia-Allut, Jose M Cabezas-Agricola, Javier Rodriguez-Garcia, Pamela V Lear, Rosa M Alvarez-San Martin, Cristina Alvarez-Escola, Ignacio Bernabeu, Clara V Alvarez
BACKGROUND: Acromegaly is produced by excess growth hormone secreted by a pituitary adenoma of somatotroph cells (ACRO). First-line therapy, surgery and adjuvant therapy with somatostatin analogs, fails in 25% of patients. There is no predictive factor of resistance to therapy. New therapies are investigated using few dispersed tumor cells in acute primary cultures in standard conditions where the cells do not grow, or using rat pituitary cell lines that do not maintain the full somatotroph phenotype...
April 8, 2019: EBioMedicine
https://read.qxmd.com/read/30914797/the-adjuvant-treatment-of-kidney-cancer-a-multidisciplinary-outlook
#2
REVIEW
Camillo Porta, Laura Cosmai, Bradley C Leibovich, Thomas Powles, Maurizio Gallieni, Axel Bex
Approximately 70% of cases of kidney cancer are localized or locally advanced at diagnosis. Among patients who undergo surgery for these cancers, 30-35% will eventually develop potentially fatal metachronous distant metastases. Effective adjuvant treatments are urgently needed to reduce the risk of recurrence of kidney cancer and of dying of metastatic disease. To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit. Only two trials of an autologous renal tumour cell vaccine and of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor sunitinib have shown positive results, but these have been criticized for methodological reasons and conflicting data, respectively...
March 26, 2019: Nature Reviews. Nephrology
https://read.qxmd.com/read/30857555/complete-response-of-renal-cell-carcinoma-vena-cava-tumor-thrombus-to-neoadjuvant-immunotherapy
#3
Craig Labbate, Ken Hatogai, Ryan Werntz, Walter M Stadler, Gary D Steinberg, Scott Eggener, Randy F Sweis
BACKGROUND: Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor...
March 11, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30788170/gastrointestinal-stromal-tumors-a-comprehensive-review
#4
REVIEW
Trisha M Parab, Michael J DeRogatis, Alexander M Boaz, Salvatore A Grasso, Paul S Issack, David A Duarte, Olivier Urayeneza, Saloomeh Vahdat, Jian-Hua Qiao, Gudata S Hinika
Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. Most GISTs present asymptomatically. They are best identified by computed tomography (CT) scan and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1. There have been many risk stratification classifications systems which are calculated based on tumor size, mitotic rate, location, and perforation. The approaches to treating GISTs are to resect primary low-risk tumors, resect high-risk primary or metastatic tumors with imatinib 400 mg daily for 12 months, or if the tumor is unresectable, neoadjuvant imatinib 400 mg daily followed by surgical resection is recommended...
February 2019: Journal of Gastrointestinal Oncology
https://read.qxmd.com/read/30758764/adjuvant-therapy-in-renal-cell-carcinoma-the-perspective-of-urologists
#5
Annabel Spek, B Szabados, J Casuscelli, C Stief, M Staehler
BACKGROUND: Until recently, there was no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) unless sunitinib was approved in the US. We evaluated clinical opinion and estimated use regarding different treatment options and patient selection of AT in RCC patients based on current scientific data and individual experience in Germany. METHODS: We conducted an anonymous survey during a national urology conference in 01/2017. Answers of 157 urologists treating RCC patients could be included...
February 13, 2019: International Journal of Clinical Oncology
https://read.qxmd.com/read/30692490/-gastrointestinal-stromal-tumor-of-the-small-intestine-with-dissemination-successfully-treated-with-surgical-resection-and-adjuvant-chemotherapy-with-sunitinib-a-case-report
#6
Shinsaku Obara, Hiroyuki Nakayama, Tatsushi Kato, Takatsugu Yamada, Yuya Nakamura, Takao Nishimura, Yoshinori Kito, Ryuji Okamura
We report the case of a 73-year-old woman with repeated recurrent small intestinal gastrointestinal stromal tumor(GIST) who was referred to our hospital for best supportive care. She underwent surgical resection 4 times and developed recurrent tumors that were resistant to imatinib. She complained of right lower abdominal pain caused by the recurrent tumor. We performed surgical resection of the tumor and the disseminated tumors synchronously. Histopathological findings of the resected specimen revealed a high-risk GIST...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://read.qxmd.com/read/30653116/complete-response-to-sunitinib-for-more-than-three-years-in-a-patient-with-a-jejunum-gastrointestinal-stromal-tumor-a-case-report
#7
Yanli Nie, Wenjia Sun, Zhihua Xiao, Shengwei Ye
RATIONALE: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is characterized by KIT mutations. Patientsresistant to 1st-line imatinib therapy are usually given sunitinib assecond-line treatment, which provides a median progression-free survival of 8 to 12 months. We report the 1st case of metastatic jejunum GIST with a KIT exon 11 deletion that showed complete response (CR) to sunitinib for more than 3 years. PATIENT CONCERNS: A 34-year-old man with advanced jejunum GIST was surgically treated upon initial diagnosis, and was histologically found to carry a high recurrence risk...
January 2019: Medicine (Baltimore)
https://read.qxmd.com/read/30636935/cost-utility-analysis-of-adjuvant-imatinib-treatment-in-patients-with-high-risk-of-recurrence-after-gastrointestinal-stromal-tumour-gist-resection-in-thailand
#8
Thanaporn Bussabawalai, Kittiphong Thiboonboon, Yot Teerawattananon
Background: Many patients develop tumour recurrence within a few years after undergoing surgical resection of gastrointestinal stromal tumours (GIST). Adjuvant imatinib treatment is recommended for patients with high risk of GIST recurrence as it can improve recurrence-free survival and overall survival of patients. This study aims to assess the cost-utility of adjuvant imatinib in patients with high risk of GIST recurrence after surgery compared with no adjuvant therapy in Thailand. Methods: A Markov model was developed to estimate lifetime costs and outcomes of using adjuvant imatinib treatment and other treatment alternatives if recurrence occurred compared with the current situation of no adjuvant therapy in high-risk patients after surgery...
2019: Cost Effectiveness and Resource Allocation: C/E
https://read.qxmd.com/read/30636586/mirna-targeting-angiogenesis-as-a-potential-therapeutic-approach-in-the-treatment-of-colorectal-cancers
#9
Forouzan Amerizadeh, Majid Khazaei, Mona Maftouh, Ramin Mardani, Afsane Bahrami
Angiogenesis refers to the formation of recent blood vessels, which is one of the characteristics of cancer progression. and it has been deliberated a putative target to the treatment of many kinds of cancers. The VEGF signaling substrate is very important for angiogenesis and is commonly high-regulated in tumors. As a result, this molecule has attracted one of the most attention of researchers to develop antiangiogenic therapies. We have presented that VEGF blockage in neoadjuvant setting via bevacizumab, aflibercept and sunitinib not only have revealed some promising benefit but also it shows a large negative outcome in the adjuvant trials...
January 10, 2019: Current Pharmaceutical Design
https://read.qxmd.com/read/30620389/association-between-age-and-sex-and-mortality-after-adjuvant-therapy-for-renal-cancer
#10
Ronac Mamtani, Xin Victoria Wang, Bishal Gyawali, Robert S DiPaola, C Neill Epperson, Naomi B Haas, Janice P Dutcher
BACKGROUND: In phase 3 trials of patients with resected high-risk renal cell carcinoma, adjuvant sunitinib has demonstrated no overall survival (OS) benefit, an uncertain disease-free survival (DFS) benefit, and increased toxicity versus placebo. To identify patients who may derive benefit or harm from adjuvant therapy, the authors assessed the effects of age and sex on treatment outcomes in the phase 3 Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Cancer (ASSURE) trial. METHODS: The authors conducted a post hoc subgroup analysis of age and sex among patients in the ASSURE trial...
January 8, 2019: Cancer
https://read.qxmd.com/read/30508155/adjuvant-sunitinib-in-patients-with-high-risk-renal-cell-carcinoma-a-closer-look
#11
E Christina Tampaki, M Kontos, R Droeser, A Tampakis
No abstract text is available yet for this article.
December 3, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://read.qxmd.com/read/30498230/pre-and-post-operative-anti-pd-l1-plus-anti-angiogenic-therapies-in-mouse-breast-or-renal-cancer-models-of-micro-or-macro-metastatic-disease
#12
Florence T H Wu, Ping Xu, Annabelle Chow, Shan Man, Janna Krüger, Kabir A Khan, Marta Paez-Ribes, Elizabeth Pham, Robert S Kerbel
BACKGROUND: There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS: This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively)...
January 2019: British Journal of Cancer
https://read.qxmd.com/read/30489037/adjuvant-therapy-after-nephrectomy-for-renal-cell-carcinoma
#13
REVIEW
Alain Ravaud
Adjuvant treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor in renal cell carcinoma after nephrectomy has been reported through three clinical trials: S-TRAC, ASSURE and PROTECT. Only S-TRAC has been significantly positive on primary end-point disease-free survival under sunitinib compared to placebo, whereas ASSURE and PROTECT did not show any gain under sunitinib, sorafenib or pazopanib. This short review presents the differences between the trials and provides hypotheses on why S-TRAC may have been positive...
November 2018: Asia-Pacific Journal of Clinical Oncology
https://read.qxmd.com/read/30464696/is-there-a-role-for-adjuvant-therapy-after-surgery-in-high-risk-for-recurrence-kidney-cancer-an-update-on-current-concepts
#14
T Sharma, C Tajzler, A Kapoor
Background: Although surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting...
October 2018: Current Oncology
https://read.qxmd.com/read/30412222/adjuvant-sunitinib-in-patients-with-high-risk-renal-cell-carcinoma-safety-therapy-management-and-patient-reported-outcomes-in-the-s-trac-trial
#15
M Staehler, R J Motzer, D J George, H S Pandha, F Donskov, B Escudier, A J Pantuck, A Patel, L DeAnnuntis, H Bhattacharyya, K Ramaswamy, G Zanotti, X Lin, M Lechuga, L Serfass, J Paty, A Ravaud
Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial. Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo...
October 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://read.qxmd.com/read/30401688/phase-iii-trial-of-adjuvant-sunitinib-in-patients-with-high-risk-renal-cell-carcinoma-exploratory-pharmacogenomic-analysis
#16
Daniel J George, Jean-Francois Martini, Michael Staehler, Robert J Motzer, Ahmed Magheli, Frede Donskov, Bernard Escudier, Sherry Li, Michelle Casey, Olga Valota, Brigitte Laguerre, Allan J Pantuck, Hardev Pandha, Anup Patel, Maria J Lechuga, Alain Ravaud
PURPOSE: In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC. EXPERIMENTAL DESIGN: Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays...
November 6, 2018: Clinical Cancer Research
https://read.qxmd.com/read/30372398/perioperative-therapy-in-renal-cell-carcinoma-what-do-we-know-what-have-we-learned-what-s-next
#17
Naomi B Haas, Robert G Uzzo
Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed...
October 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://read.qxmd.com/read/30345423/adjuvant-antiangiogenic-agents-in-post-nephrectomy-renal-cell-carcinoma-a-systematic-review-and-meta-analysis
#18
Mohamad B Sonbol, Belal Firwana, Talal Hilal, Zhen Wang, Diana Almader-Douglas, Richard W Joseph, Thai H Ho
Context: The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. Objective: To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy. Evidence acquisition: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients...
June 2018: European Urology Oncology
https://read.qxmd.com/read/30187355/immune-checkpoint-inhibitors-toward-new-paradigms-in-renal-cell-carcinoma
#19
REVIEW
Ronan Flippot, Bernard Escudier, Laurence Albiges
Immune modulatory treatment regimens, led by immune checkpoint inhibitors, have transformed the treatment of clear-cell renal cell carcinoma. First-in-class, the PD-1 inhibitor nivolumab improved overall survival in advanced renal cell carcinoma following prior anti-angiogenic therapy, an important shift in the management of clear-cell renal cell carcinoma. Further improvements of long-term outcomes will be driven by combinations in the first-line setting, including PD-1/PD-L1 associated with antiangiogenic therapies, or PD1/PD-L1 inhibitors with other immune checkpoint inhibitors such as anti-CTLA-4, anti-LAG-3 or TIM-3 targeted therapies...
September 2018: Drugs
https://read.qxmd.com/read/30148828/adjuvant-treatment-in-renal-cell-carcinoma
#20
REVIEW
Nazli Dizman, Jacob J Adashek, JoAnn Hsu, Paulo G Bergerot, Cristiane D Bergerot, Sumanta K Pal
In parallel with advances in the treatment of metastatic renal cell carcinoma (RCC), multiple adjuvant treatments have been tested for RCC. Adjuvant approaches now extend beyond conventional immunotherapies, such as interferon alfa and interleukins, to targeted therapies and immune checkpoint inhibitors. Most treatment approaches before the targeted treatment era did not improve patient outcomes, or study results were mixed. For example, a recent study found that disease-free survival was longer with sunitinib than with placebo in high-risk clear cell RCC, which led to the regulatory approval of sunitinib...
August 2018: Clinical Advances in Hematology & Oncology: H&O
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