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pancreatic adenocarcinoma chemotherapy

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https://www.readbyqxmd.com/read/28817370/conko-005-adjuvant-chemotherapy-with-gemcitabine-plus-erlotinib-versus-gemcitabine-alone-in-patients-after-r0-resection-of-pancreatic-cancer-a-multicenter-randomized-phase-iii-trial
#1
Marianne Sinn, Marcus Bahra, Torsten Liersch, Klaus Gellert, Helmut Messmann, Wolf Bechstein, Dirk Waldschmidt, Lutz Jacobasch, Martin Wilhelm, Bettina M Rau, Robert Grützmann, Arndt Weinmann, Georg Maschmeyer, Uwe Pelzer, Jens M Stieler, Jana K Striefler, Michael Ghadimi, Sven Bischoff, Bernd Dörken, Helmut Oettle, Hanno Riess
Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m(2) days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles...
August 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28817187/second-line-treatment-in-patients-with-pancreatic-ductal-adenocarcinoma-a-meta-analysis
#2
Mohamad Bassam Sonbol, Belal Firwana, Zhen Wang, Diana Almader-Douglas, Mitesh J Borad, Issam Makhoul, Ramesh K Ramanathan, Daniel H Ahn, Tanios Bekaii-Saab
BACKGROUND: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC. METHODS: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28811332/de-novo-lipid-synthesis-facilitates-gemcitabine-resistance-through-endoplasmic-reticulum-stress-in-pancreatic-cancer
#3
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina CHaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean L Grem, Aaron Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single agent therapy for pancreatic cancer. While the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging TCGA dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28808501/evolving-treatment-landscape-for-early-and-advanced-pancreatic-cancer
#4
REVIEW
Sally C Lau, Winson Y Cheung
Pancreatic ductal adenocarcinoma is an infrequent cancer with a high disease related mortality rate, even in the context of early stage disease. Until recently, the rate of death from pancreatic cancer has remained largely similar whereby gemcitabine monotherapy was the mainstay of systemic treatment for most stages of disease. With the discovery of active multi-agent chemotherapy regimens, namely FOLFIRINOX and gemcitabine plus nab-paclitaxel, the treatment landscape of pancreatic cancer is slowly evolving...
July 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#5
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782087/germline-brca-mutations-in-asian-patients-with-pancreatic-adenocarcinoma-a-prospective-study-evaluating-risk-category-for-genetic-testing
#6
Kyoungmin Lee, Changhoon Yoo, Kyu-Pyo Kim, Kyoung-Jin Park, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee, Woochang Lee, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Song Cheol Kim, Baek-Yeol Ryoo
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy...
August 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28776577/pathologic-assessment-of-gastrointestinal-tract-and-pancreatic-carcinoma-after-neoadjuvant-therapy
#7
REVIEW
Reetesh K Pai, Rish K Pai
Neoadjuvant therapy is increasingly used to treat patients with a wide variety of malignancies. Histologic evaluation of treated specimens provides important prognostic information and may guide subsequent chemotherapy. Neoadjuvant therapy is commonly employed in the treatment of locally advanced rectal adenocarcinoma, hepatic colorectal metastases, esophageal/esophagogastric junction carcinoma, and pancreatic ductal adenocarcinoma. Numerous tumor regression schemes have been used in these tumors and standardized approaches to evaluate these specimens are needed...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28774899/89zr-anti-%C3%AE-h2ax-tat-but-not-18f-fdg-allows-early-monitoring-of-response-to-chemotherapy-in-a-mouse-model-of-pancreatic-ductal-adenocarcinoma
#8
James C Knight, Michael J Mosley, Luisa Contreras Bravo, Veerle Kersemans, Philip D Allen, Somnath Mukherjee, Eric O'Neill, Bart Cornelissen
Purpose: Late-stage, unresectable pancreatic ductal adenocarcinoma (PDAC) is largely resistant to chemotherapy and consequently has a very poor 5-year survival rate of < 5%. The ability to assess the efficacy of a treatment soon after its initiation would enable rapid switching to potentially more effective therapies if the current treatment is found to be futile. We have evaluated the ability of the PET imaging agent, (89)Zr-anti-γH2AX-TAT, to monitor DNA damage in response to fluouracil (5-FU), gemcitabine, or capecitabine treatment in a mouse model of pancreatic cancer...
August 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#9
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28756944/laparoscopic-distal-pancreatectomy-for-pancreatic-ductal-adenocarcinoma-long-term-oncologic-outcomes-after-standard-resection
#10
Mushegh A Sahakyan, Song Cheol Kim, Dyre Kleive, Airazat M Kazaryan, Ki Byung Song, Dejan Ignjatovic, Trond Buanes, Bård I Røsok, Knut Jørgen Labori, Bjørn Edwin
BACKGROUND: Surgical resection is the only curative option in patients with pancreatic ductal adenocarcinoma. Little is known about the oncologic outcomes of laparoscopic distal pancreatectomy. This bi-institutional study aimed to examine the long-term oncologic results of standard laparoscopic distal pancreatectomy in a large cohort of patients with pancreatic ductal adenocarcinoma. METHODS: From January 2002 to March 2016, 207 patients underwent standard laparoscopic distal pancreatectomy for with pancreatic ductal adenocarcinoma at Oslo University Hospital-Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, Republic of Korea)...
July 27, 2017: Surgery
https://www.readbyqxmd.com/read/28750659/alliance-for-clinical-trials-in-oncology-alliance-trial-a021501-preoperative-extended-chemotherapy-vs-chemotherapy-plus-hypofractionated-radiation-therapy-for-borderline-resectable-adenocarcinoma-of-the-head-of-the-pancreas
#11
Matthew H G Katz, Fang-Shu Ou, Joseph M Herman, Syed A Ahmad, Brian Wolpin, Robert Marsh, Spencer Behr, Qian Shi, Michael Chuong, Lawrence H Schwartz, Wendy Frankel, Eric Collisson, Eugene J Koay, JoLeen M Hubbard, James L Leenstra, Jeffrey Meyerhardt, Eileen O'Reilly
BACKGROUND: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and 64% of operations achieved an R0 resection. However, the individual contributions of preoperative chemotherapy and radiation therapy to therapeutic outcome remain poorly defined...
July 27, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28747265/pancreatic-adenocarcinoma-effects-of-neoadjuvant-therapy-on-post-pancreatectomy-outcomes-an-american-college-of-surgeons-national-surgical-quality-improvement-program-targeted-variable-review
#12
Nicholas M Czosnyka, Andrew J Borgert, Travis J Smith
BACKGROUND: As the incidence of pancreatic adenocarcinoma increases, so has the utilization of neoadjuvant therapy. The objective of this study was to evaluate outcomes in patients undergoing neoadjuvant therapy or surgery first for pancreatic adenocarcinoma. METHODS: The ACS-NSQIP 2014-2015 targeted pancreatectomy variables were queried for patients with pancreatic adenocarcinoma who underwent resection. Outcomes of those receiving neoadjuvant therapy were compared to surgery first using a multivariate, logistic regression model...
July 23, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28736631/shifting-paradigm-of-developing-biologics-for-the-treatment-of-pancreatic-adenocarcinoma
#13
REVIEW
Ying Zeng, Agnieszka A Rucki, Xu Che, Lei Zheng
Pancreatic adenocarcinoma is still widely considered as a deadly disease even though there are substantial therapeutic developments in the past decade. Using combinational chemotherapy regimens, represented by gemcitabine plus nab-paclitaxel and FOLFIRINOX, was able to improve overall survival in patients with advanced disease to a limited extent. It has been a challenge to develop targeted therapies that are focused on the neoplasm cells of pancreatic adenocarcinoma. Recently, targeting the stroma and immune compartments of pancreatic adenocarcinoma has shown promising results...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28722678/optimal-adjuvant-chemotherapy-for-resected-pancreatic-adenocarcinoma-a-systematic-review-and-network-meta-analysis
#14
Jian-Bo Xu, Bin Jiang, Ya Chen, Fu-Zhen Qi, Jian-Huai Zhang, Hang Yuan
Adjuvant chemotherapy improves survival in patients with resected pancreatic cancer but the optimal regimen remains unclear. We aim to compare all possible adjuvant chemotherapy in terms of overall survival and toxic effects. Pubmed, Trial registries and Cochrane library databases for randomized controlled trials were searched until November 2016. Thirteen trials were included for network analysis and the hazard ratios (HRs) for survival and odds ratios for toxic effects were assessed via Aggregate Data Drug Information System software...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718038/reappraisal-of-staging-laparoscopy-for-patients-with-pancreatic-adenocarcinoma-a-contemporary-analysis-of-1001-patients
#15
Zhi Ven Fong, Donna Marie L Alvino, Carlos Fernández-Del Castillo, Winta T Mehtsun, Ilaria Pergolini, Andrew L Warshaw, David C Chang, Keith D Lillemoe, Cristina R Ferrone
BACKGROUND: Recent advances in imaging and the increasing use of neoadjuvant therapy puts the contemporary utility of staging laparoscopy for patients with pancreatic adenocarcinoma (PDAC) into question. This study aimed to develop a prognostic score to optimize prevention of an unnecessary laparotomy and minimize the rate for unnecessary laparoscopy. METHODS: Clinicopathologic data were evaluated for all patients undergoing surgical intervention for PDAC between 2001 and 2015, who were stratified into group 1 (2001-2008) and group 2 (2009-2014)...
July 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28716115/resectable-adenocarcinoma-developing-in-the-remnant-pancreas-7%C3%A2-years-after-partial-pancreatoduodenectomy-for-invasive-ductal-adenocarcinoma-of-the-pancreas-a-case-report
#16
Lina Frei, Ruedi Stieger, Christian Bayerl, Stefan Breitenstein, Ralph F Staerkle
BACKGROUND: Pancreatic adenocarcinoma still has an excessively high mortality rate and resection is the only potentially curative treatment. The postoperative 5-year survival rate is approximately 20% and recurrence develops generally within 2 years. We report a case of a localized recurrent pancreatic adenocarcinoma in the remnant pancreas, 7 years after initial resection. CASE PRESENTATION: In 2008 an abdominal computed tomography scan showed a mass in the pancreas of a 70-year-old white woman, who presented with occlusive jaundice and abdominal pain in her right upper quadrant...
July 17, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28714519/circulating-regulatory-t-cell-subsets-predict-overall-survival-of-patients-with-unresectable-pancreatic-cancer
#17
Chen Liu, He Cheng, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Quanxing Ni, Xianjun Yu
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28710540/home-based-exercise-during-preoperative-therapy-for-pancreatic-cancer
#18
An Ngo-Huang, Nathan H Parker, Xuemei Wang, Maria Q B Petzel, David Fogelman, Keri L Schadler, Eduardo Bruera, Jason B Fleming, Jeffrey E Lee, Matthew H G Katz
PURPOSE: Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy. METHODS: Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled...
July 15, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28708929/stereotactic-body-radiotherapy-for-unresected-pancreatic-cancer-a-nationwide-review
#19
Susanna W L de Geus, Mariam F Eskander, Gyulnara G Kasumova, Sing Chau Ng, Tara S Kent, Joseph D Mancias, Mark P Callery, Anand Mahadevan, Jennifer F Tseng
BACKGROUND: The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. METHODS: The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012...
July 14, 2017: Cancer
https://www.readbyqxmd.com/read/28708229/adjuvant-chemoradiotherapy-gemcitabine-based-in-pancreatic-adenocarcinoma-the-pisa-university-experience
#20
Aldo Sainato, Sabrina Montrone, Francesco Pasqualetti, Marianna Coppola, Nunzia L V Cernusco, Marco Panichi, Alessandra Gonnelli, Enrico Vasile, Riccardo Morganti, Alfredo Falcone, Ugo Boggi, Fabiola Paiar
INTRODUCTION: The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. METHODS: 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly)...
July 11, 2017: Tumori
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