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Panitumumab

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https://www.readbyqxmd.com/read/28531891/dual-inhibition-of-egfr-and-vegf-in-heavily-pretreated-patients-with-metastatic-colorectal-cancer
#1
Finn Ole Larsen, Alice Markussen, Dorte Nielsen, Bonnie Colville-Ebeling, Lene B Riis, Benny V Jensen
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. METHODS: All patients had KRAS wild-type metastatic colorectal cancer and had previously received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well...
May 23, 2017: Oncology
https://www.readbyqxmd.com/read/28507280/molecular-dissection-of-effector-mechanisms-of-ras-mediated-resistance-to-anti-egfr-antibody-therapy
#2
Stefan Kasper, Henning Reis, Sophie Ziegler, Silke Nothdurft, Andre Mueller, Moritz Goetz, Marcel Wiesweg, Jeannette Phasue, Saskia Ting, Sarah Wieczorek, Anna Even, Karl Worm, Michael Pogorzelski, Sandra Breitenbuecher, Johannes Meiler, Andreas Paul, Tanja Trarbach, Kurt Werner Schmid, Frank Breitenbuecher, Martin Schuler
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486761/panitumumab-interaction-with-tas-102-leads-to-combinational-anticancer-effects-via-blocking-of-egfr-mediated-tumor-response-to-trifluridine
#3
Yuji Baba, Toshiya Tamura, Yoshihiko Satoh, Masamitsu Gotou, Hiroshi Sawada, Shunsuke Ebara, Kazunori Shibuya, Jumpei Soeda, Kazuhide Nakamura
Panitumumab is a monoclonal antibody developed against the human epidermal growth factor receptor (EGFR). TAS-102 is a novel chemotherapeutic agent containing trifluridine (FTD) as the active cytotoxic component. Both panitumumab and TAS-102 have been approved for the treatment of metastatic colorectal cancer. In this study, we revealed the mechanism underlying the anticancer effects of panitumumab/TAS-102 combination using preclinical models. Panitumumab/FTD co-treatment showed additive antiproliferative effects in LIM1215 and synergistic antiproliferative effects in SW48 colon cancer cells...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28456787/predictive-blood-plasma-biomarkers-for-egfr-inhibitor-induced-skin-rash
#4
Vivien Hichert, Catharina Scholl, Michael Steffens, Tanusree Paul, Christian Schumann, Stefan Rüdiger, Stefan Boeck, Volker Heinemann, Volker Kächele, Thomas Seufferlein, Julia Stingl
Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28449055/primary-tumor-sidedness-has-an-impact-on-prognosis-and-treatment-outcome-in-metastatic-colorectal-cancer-results-from-two-randomized-first-line-panitumumab-studies
#5
N Boeckx, R Koukakis, K Op de Beeck, C Rolfo, G Van Camp, S Siena, J Tabernero, J-Y Douillard, T André, M Peeters
Background: : Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Material and methods: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients...
April 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28439399/posterior-reversible-encephalopathy-syndrome-with-colitis-in-a-patient-treated-with-panitumumab
#6
Céline Blaye, Xavier Buy, Marine Gross-Goupil, Didier Vincent, Claire Jamet, Paul Sargos, Stéphane Culine, Guilhem Roubaud
No abstract text is available yet for this article.
April 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/28435294/patient-considerations-in-metastatic-colorectal-cancer-role-of-panitumumab
#7
REVIEW
Jane E Rogers
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28424871/final-analysis-of-the-randomised-peak-trial-overall-survival-and-tumour-responses-during-first-line-treatment-with-mfolfox6-plus-either-panitumumab-or-bevacizumab-in-patients-with-metastatic-colorectal-carcinoma
#8
Fernando Rivera, Meinolf Karthaus, J Randolph Hecht, Isabel Sevilla, Frédéric Forget, Gianpiero Fasola, Jean-Luc Canon, Xuesong Guan, Gaston Demonty, Lee S Schwartzberg
PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective...
April 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28418176/panitumumab-conjugated-pt-drug-nanomedicine-for-enhanced-efficacy-of-combination-targeted-chemotherapy-against-colorectal-cancer
#9
Ming-Hsien Tsai, Chao-Hsuan Pan, Cheng-Liang Peng, Ming-Jium Shieh
Targeted combination chemotherapy (TCT) has recently been used to increase the induction of tumor cell death. In particular, the combination of Panitumumab and the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that overexpress epidermal growth factor receptors, and significantly greater efficacy is observed than with either drug alone. However, low accumulation of Pt drug in tumor sites prevents achievement of ideal efficacy...
April 18, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28404754/therapeutic-response-of-metastatic-colorectal-cancer-harboring-a-kras-missense-mutation-after-combination-chemotherapy-with-the-egfr-inhibitor-panitumumab
#10
Emil Lou, Donna D'Souza, Andrew C Nelson
Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28403233/cost-effectiveness-of-cetuximab-and-panitumumab-for-chemotherapy-refractory-metastatic-colorectal-cancer
#11
Adriana Camargo Carvalho, Frederico Leal, Andre Deeke Sasse
BACKGROUND: Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). METHODS: A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC...
2017: PloS One
https://www.readbyqxmd.com/read/28399109/tyrosine-kinase-targeting-drugs-associated-heart-failure
#12
N Gronich, I Lavi, O Barnett-Griness, W Saliba, D R Abernethy, G Rennert
BACKGROUND: The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF). METHODS: A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28379722/clinical-pathways-management-of-quality-and-cost-in-oncology-networks-in-the-metastatic-colorectal-cancer-setting
#13
Peter G Ellis, Bert H O'Neil, Martin F Earle, Stephanie McCutcheon, Hans Benson, Melinda Krebs, Kathy Lokay, Amanda Barry
PURPOSE: Via Pathways (clinical pathways for cancer) provide evidence-based guidance for specific patient presentations based on the merit of efficacy, then toxicity, and finally cost (if efficacy and toxicity are comparable). We evaluated the impact of a change to the guidance in the metastatic colorectal cancer (mCRC) setting across two large, integrated health networks. METHODS: Cetuximab and panitumumab were determined to have equal efficacy in the treatment of mCRC with no significant difference in toxicity based on recent data from key clinical studies...
May 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28375604/structure-directed-and-tailored-diversity-synthetic-antibody-libraries-yield-novel-anti-egfr-antagonists
#14
Shane Miersch, Bharathikumar Vellalore Maruthachalam, C Ronald Geyer, Sachdev S Sidhu
We tested whether grafting an interaction domain into the hypervariable loop of a combinatorial antibody library could promote targeting to a specific epitope. Formation of the epidermal growth factor receptor (EGFR) signaling heterodimer involves extensive contacts mediated by a "dimerization loop." We grafted the dimerization loop into the third hypervariable loop of a synthetic antigen-binding fragment (Fab) library and diversified other loops using a tailored diversity strategy. This structure-directed Fab library and a naı̈ve synthetic Fab library were used to select Fabs against EGFR...
April 4, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#15
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28284575/mfolfox6-plus-panitumumab-versus-5-fu-lv-plus-panitumumab-after-six-cycles-of-frontline-mfolfox6-plus-panitumumab-a-randomized-phase-ii-study-of-patients-with-unresectable-or-advanced-recurrent-ras-wild-type-colorectal-carcinoma-sapphire-study-design-and%C3%A2-rationale
#16
Naoki Nagata, Hideyuki Mishima, Shuichi Kurosawa, Koji Oba, Junichi Sakamoto
BACKGROUND: In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option...
March 1, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28282789/a-randomized-phase-iii-study-of-combining-erlotinib-with-bevacizumab-and-panitumumab-versus-erlotinib-alone-as-second-line-therapy-for-chinese-patients-with-non-small-cell-lung-cancer
#17
Ying Wang, Hui Wang, Yiling Jiang, Yaping Zhang, Xiaoyan Wang
PURPOSE: In this phase III clinical study, we assessed the clinical outcomes of combining erlotinib with bevacizumab and panitumumab as second-line chemotherapy for patients with non-small-cell lung cancer (NSCLC). METHODS: Chinese NSCLC patients, who received first-line platinum-based chemotherapy but still experienced disease progression, were assigned to receive second-line treatment of erlotinib plus bevacizumab and panitumumab (arm I), or erlotinib plus placebo (arm II)...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#18
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28245681/-does-the-sidedness-determine-the-first-line-treatment-of-irresectable-metastatic-colorectal-cancer
#19
Tamás Kullmann, István Sipőcz, Tamás Pintér
INTRODUCTION AND AIM: Median life expectancy of non-resectable metastatic colorectal cancer may surpass three years. However, several points of the treatment strategy are subject of ongoing debate. Optimal sequence of targeted agents is not elucidated either. Based on retrospective analyses of six clinical studies and a metaanalysis, the superiority of anti-EGFR agents such as cetuximab and panitumumab over anti-VEGF bevacizumab has been proposed in the treatment of left sided tumours...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28242452/top-down-analysis-of-immunoglobulin-g-isotypes-1-and-2-with-electron-transfer-dissociation-on-a-high-field-orbitrap-mass-spectrometer
#20
Luca Fornelli, Daniel Ayoub, Konstantin Aizikov, Xiaowen Liu, Eugen Damoc, Pavel A Pevzner, Alexander Makarov, Alain Beck, Yury O Tsybin
The increasing importance of immunoglobulins G (IgGs) as biotherapeutics calls for improved structural characterization methods designed for these large (~150kDa) macromolecules. Analysis workflows have to be rapid, robust, and require minimal sample preparation. In a previous work we showed the potential of Orbitrap Fourier transform mass spectrometry (FTMS) combined with electron transfer dissociation (ETD) for the top-down investigation of an intact IgG1, resulting in ~30% sequence coverage. Here, we describe a top-down analysis of two IgGs1 (adalimumab and trastuzumab) and one IgG2 (panitumumab) performed with ETD on a mass spectrometer equipped with a high-field Orbitrap mass analyzer...
April 21, 2017: Journal of Proteomics
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