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https://www.readbyqxmd.com/read/29135265/evaluation-of-early-therapeutic-effects-after-near-infrared-photoimmunotherapy-nir-pit-using-luciferase-luciferin-photon-counting-and-fluorescence-imaging
#1
Yasuhiro Maruoka, Tadanobu Nagaya, Yuko Nakamura, Kazuhide Sato, Fusa Ogata, Shuhei Okuyama, Peter L Choyke, Hisataka Kobayashi
Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer treatment that induces highly selective immunogenic cell death. It is based on an antibody-photo-absorber conjugate (APC) that is activated by NIR light. The purpose of this study was to investigate the effects of NIR-PIT as measured by luciferase-luciferin photon-counting and fluorescence imaging. Six days after subcutaneous injection of A431-luc-GFP cells tumors formed in a xenograft mouse model. The EGFR-targeting antibody, panitumumab was conjugated to the photoabsorber, IRDye-700DX (pan-IR700) and was intravenously administered to tumor-bearing mice...
November 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29101848/human-fc-receptor-like-5-distinguishes-igg2-disulfide-isoforms-and-deamidated-charge-variants
#2
Oyeleye Alabi, Jessica Dement-Brown, Mate Tolnay
Human Fc receptor-like 5 (FCRL5) is a novel IgG receptor. We reported that IgG2 samples display a thousand-fold range affinity for FCRL5, indicating that attributes beyond the isotype affect binding. We hypothesized that the complex interaction could be exploited to identify distinct changes in the IgG2 molecule. We investigated using surface plasmon resonance two factors that might affect the interaction between IgG2 and FCRL5; heterogeneity related to disulfide isoforms and charge variants. We found that panitumumab and denosumab samples enriched for the more flexible A disulfide isoform bound FCRL5 with two-fold and 82-fold higher apparent affinity, respectively, than the B isoform...
November 1, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29096990/survival-outcomes-in-patients-with-ras-wild-type-metastatic-colorectal-cancer-classified-according-to-k%C3%A3-hne-prognostic-category-and-braf-mutation-status
#3
Salvatore Siena, Fernando Rivera, Julien Taieb, Marc Peeters, Hans Prenen, Reija Koukakis, Gaston Demonty, Claus-Henning Köhne
BACKGROUND: Köhne prognostic score is used to classify patients with metastatic colorectal cancer (mCRC) as high, intermediate, or low risk. Using data from 2 phase III trials, we analyzed survival in patients categorized according to Köhne prognostic category and virus-induced rapidly accelerated fibrosarcoma murine sarcoma viral oncogene homolog B (BRAF) mutation. PATIENTS AND METHODS: PRIME (Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy) (first-line) and 20050181 (second-line) were studies of chemotherapy with or without panitumumab...
September 28, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29080924/exploratory-analyses-assessing-the-impact-of-early-tumour-shrinkage-and-depth-of-response-on-survival-outcomes-in-patients-with-ras-wild-type-metastatic-colorectal-cancer-receiving-treatment-in-three-randomised-panitumumab-trials
#4
Julien Taieb, Fernando Rivera, Salvatore Siena, Meinolf Karthaus, Manuel Valladares-Ayerbes, Javier Gallego, Michael Geissler, Reija Koukakis, Gaston Demonty, Marc Peeters
PURPOSE: To report exploratory analyses of early tumour shrinkage (ETS) and depth of response (DpR) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), receiving the first-line treatment in three randomised panitumumab trials. METHODS: Data from the PRIME (NCT00364013), PEAK (NCT00819780) and PLANET (NCT00885885) studies were included. Median DpR, the proportion of patients achieving ETS ≥ 20% or ≥ 30% at week 8, and the impact of ETS and DpR (including by category) on outcome were analysed...
October 28, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29075780/association-of-tumor-her3-messenger-rna-expression-with-panitumumab-efficacy-in-advanced-colorectal-cancer
#5
Jenny F Seligmann, Ace J Hatch, Susan D Richman, Faye Elliott, Bart Jacobs, Sarah Brown, Herbert Hurwitz, Jennifer H Barrett, Philip Quirke, Andrew B Nixon, Matthew T Seymour
Importance: Epidermal growth factor receptor (EGFR) (HER1) signaling depends on ligand binding and dimerization with itself or other HER receptors. We previously showed in a randomized trial that high EGFR ligand expression is predictive of panitumumab benefit in advanced colorectal cancer. Tumor expression of HER3 may further refine the RAS wild-type (wt) population benefitting from anti-EGFR agents. Objective: To examine HER3 messenger RNA expression as a prognostic and predictive biomarker for anti-EGFR therapy in a randomized clinical trial of panitumumab...
October 26, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29075194/pharmacogenomics-dna-biomarkers-in-colorectal-cancer-current-update
#6
REVIEW
Nurul-Syakima Ab Mutalib, Najwa F Md Yusof, Shafina-Nadiawati Abdul, Rahman Jamal
Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29073892/multiple-criteria-decision-analysis-in-the-context-of-health-technology-assessment-a-simulation-exercise-on-metastatic-colorectal-cancer-with-multiple-stakeholders-in-the-english-setting
#7
Aris Angelis, Gilberto Montibeller, Daniel Hochhauser, Panos Kanavos
BACKGROUND: Multiple criteria decision analysis (MCDA) has appeared as a methodology to address limitations of economic evaluation in health technology assessment (HTA), however there are limited empirical evidence from real world applications. The aim of this study is to test in practice a recently developed MCDA methodological framework known as Advance Value Framework (AVF) through a proof-of-concept case study engaging multiple stakeholders. METHODS: A multi-attribute value theory methodological process was adopted involving problem structuring, model building, model assessment and model appraisal phases...
October 26, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/29066705/-anti-egfr-antibody-combination-chemotherapy-was-effective-against-locally-advanced-ascending-colon-cancer-as-well-as-a-recurrent-lesion-a-case-report
#8
Yasufumi Yamada, Hajime Yokomizo, Yuki Yano, Sachiyo Okayama, Masaya Satake, Arika Ida, Takebumi Usui, Kentaro Yamaguchi, Shunichi Shiozawa, Kazuhiko Yoshimatsu, Takeshi Shimakawa, Takao Katsube, Yoshihiko Naritaka, Hiroyuki Kato
Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29062621/rectal-cancer-in-the-eye-a-case-report-of-orbital-metastasis
#9
Mohammed Nabeel, Rehan Farooqi, Mahsa Mohebtash, Rupak Desai, Uvesh Mansuri, Smit Patel, Jinal Patel, Vinshi Naz Khan
Orbital metastasis from colorectal cancer is extremely rare. In this case report, we describe a 48-year-old woman who presented with recurrent severe headaches and new onset constipation with no known history of cancer. After vigilant workup, imaging, and biopsies, she was diagnosed with orbital metastasis from a primary rectal carcinoma. She was started on chemotherapy and radiation therapy. Her chemotherapy regimen consisted of FLOX (leucovorin + fluorouracil + oxaliplatin), along with panitumumab, which she tolerated well...
August 21, 2017: Curēus
https://www.readbyqxmd.com/read/29061833/anti-epidermal-growth-factor-receptor-antibody-readministration-in-chemorefractory-metastatic-colorectal-cancer
#10
Tatsuhiro Kajitani, Akitaka Makiyama, Shuji Arita, Hozumi Shimokawa, Hisanobu Oda, Tsuyoshi Shirakawa, Eishi Baba, Taito Esaki
BACKGROUND/AIM: Readministration of anti-epidermal growth factor receptor (EGFR) antibody for metastatic colorectal cancer (mCRC) after disease progression remains to be determined. PATIENTS AND METHODS: Readministration of anti-EGFR antibody in mCRC patients previously refractory to anti-EGFR antibody was prospectively observed. RESULTS: A total of thirteen patients with a median age of 60-years old and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29022151/comparative-safety-of-targeted-therapies-for-metastatic-colorectal-cancer-between-elderly-and-younger-patients-a-study-using-the-international-pharmacovigilance-database
#11
Amandine Gouverneur, Pauline Claraz, Marine Rousset, Mickaël Arnaud, Annie Fourrier-Réglat, Antoine Pariente, Thomas Aparicio, Ghada Miremont-Salamé, Pernelle Noize
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly. OBJECTIVE: This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life. PATIENTS AND METHODS: An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed...
October 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29021377/a-comprehensive-review-of-sequencing-and-combination-strategies-of-targeted-agents-in-metastatic-colorectal-cancer
#12
REVIEW
Kristen K Ciombor, Tanios Bekaii-Saab
The emergence of targeted therapies for the treatment of metastatic colorectal cancer (mCRC) has considerably improved survival, but has resulted in a dilemma of identifying the optimal sequence and combination of various agents in the mCRC treatment landscape. A number of cytotoxic agents, including irinotecan, oxaliplatin, 5-fluorouracil, capecitabine, and TAS-102, are available for treatment of mCRC. Additionally, whereas patients harboring rat sarcoma viral oncogene homolog (RAS)-wild type mCRC can be treated with the anti-epidermal growth factor receptor antibodies cetuximab and panitumumab or antiangiogenic agents (bevacizumab, ziv-aflibercept, and ramucirumab), patients with RAS-mutant mCRC are limited to antiangiogenic agents as biologic options...
October 11, 2017: Oncologist
https://www.readbyqxmd.com/read/28981524/neutral-evolution-of-drug-resistant-colorectal-cancer-cell-populations-is-independent-of-their-kras-status
#13
Krastan B Blagoev, Julia Wilkerson, Mauricio Burotto, Chul Kim, Edward Espinal-Domínguez, Pilar García-Alfonso, Meghna Alimchandani, Markku Miettinen, Montserrat Blanco-Codesido, Tito Fojo
Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1) do mutations in the target/pathway confer resistance? (2) Are these mutations pre-existing? (3) What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC). We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices...
2017: PloS One
https://www.readbyqxmd.com/read/28978055/therapeutic-efficacy-of-sym004-a-mixture-of-two-anti-egfr-antibodies-in-human-colorectal-cancer-with-acquired-resistance-to-cetuximab-and-met-activation
#14
Stefania Napolitano, Giulia Martini, Erika Martinelli, Valentina Belli, Alessia Parascandolo, Mikko O Laukkanen, Vincenzo Sforza, Floriana Morgillo, Davide Ciardiello, Fortunato Ciardiello, Teresa Troiani
PURPOSE: Cetuximab and panitumumab have an effective therapeutic response in a subset of RAS Wild-Type (WT) metastatic colorectal cancers (mCRCs). Despite molecular-driven selection, all patients do not respond to epidermal growth factor receptor (EGFR) inhibitors and the onset of secondary resistance limits their clinical benefit. EXPERIMENTAL DESIGN: We tested, in vitro and in vivo, the effect of SYM004, a 1:1 mixture of two recombinant human-mouse chimeric monoclonal antibodies (mAbs) directed against non-overlapping epitopes of the EGFR, on CRC models with acquired resistance to cetuximab...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28950807/durable-complete-remission-following-anti-egfr-antibodies-in-recurrent-metastatic-colorectal-cancer
#15
Etienne Boudrias-Dalle, Magali Cloutier, Marjorie Harvey, Guy Leblanc, Olivier Besner-Morin, Jean-Philippe Adam
In this case report, we describe a patient who remains in complete remission two years after the discontinuation of anti-EGFR monotherapy as a third-line treatment, accompanied by persistent severe hypomagnesemia. A 45-year-old Caucasian woman with mCRC started chemotherapy with weekly cetuximab. After ten months of treatment, the therapy was stopped because the patient had persistent grade III hypomagnesemia despite amiloride, oral, and intravenous magnesium. A month later, the patient was switched to panitumumab 6 mg/kg every two weeks for four additional months to avoid weekly visits to the clinic...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28945848/dynamic-molecular-analysis-and-clinical-correlates-of-tumor-evolution-within-a-phase-2-trial-of-panitumumab-based-therapy-in-metastatic-colorectal-cancer
#16
S Siena, A Sartore-Bianchi, R Garcia-Carbonero, M Karthaus, D Smith, J Tabernero, E Van Cutsem, X Guan, M Boedigheimer, A Ang, B Twomey, B A Bach, A S Jung, A Bardelli
Background: Mutations in rat sarcoma ( RAS) genes may be a mechanism of secondary resistance in EGFR inhibitor-treated patients. Tumor-tissue biopsy testing has been the standard for evaluating mutational status; however, plasma testing of cell-free DNA has been shown to be a more sensitive method for detecting clonal evolution. Materials and Methods: Archival pre- and post-treatment tumor biopsy samples from a phase 2 study of panitumumab in combination with irinotecan in patients with metastatic colorectal cancer (mCRC) that also collected plasma samples before, during, and after treatment were analyzed for emergence of mutations during/post-treatment by next-generation sequencing (NGS) and BEAMing...
September 4, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28932126/dermopathy-associated-with-cetuximab-and-panitumumab-investigation-of-the-usefulness-of-moisturizers-in-its-management
#17
Shoichi Watanabe, Motoki Nakamura, Hiroki Takahashi, Masayasu Hara, Kei Ijichi, Daisuke Kawakita, Akimichi Morita
AIMS: Limited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients. PATIENTS AND METHODS: Patients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid(®)), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28913158/dosimetry-and-first-human-experience-with-89-zr-panitumumab
#18
Liza Lindenberg, Stephen Adler, Ismail B Turkbey, Francesca Mertan, Anita Ton, Khanh Do, Shivaani Kummar, Esther Mena Gonzalez, Sibaprasad Bhattacharyya, Paula M Jacobs, Peter Choyke
(89)Zr-panitumumab is a novel immuno-PET radiotracer. A fully humanized IgG2 antibody, panitumumab binds with high affinity to the extracellular ligand binding domain of EGFR. Immuno-PET with radiolabeled panitumumab is a non-invasive method that could characterize EGFR expression in tumors and metastatic lesions. It might also assist in selecting patients likely to benefit from targeted therapy as well as monitor response and drug biodistribution for dosing guidance. Our objective was to calculate the maximum dosing for effective imaging with minimal radiation exposure in a small subset...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28870789/panitumumab-in-combination-with-preoperative-radiation-therapy-in-patients-with-locally-advanced-ras-wild-type-rectal-cancer-results-of-the-multicenter-explorative-single-arm-phase-2-study-neorit
#19
MULTICENTER STUDY
Kirsten Merx, Uwe M Martens, Melanie Kripp, Thomas Hoehler, Michael Geissler, Timo Gaiser, Sabine Mai, Peter Kienle, Sebastian Belle, Christoph Plöger, Udo Hieber, Frederik Wenz, Stefan Post, Ralf D Hofheinz
PURPOSE: Studies investigating combinations of anti-epidermal growth factor receptor monoclonal antibodies such as panitumumab or cetuximab with standard chemoradiation therapy protocols in rectal cancer have yielded disappointing results. Because of the supposed negative interaction of epidermal growth factor receptor inhibition and chemoradiation therapy, we conducted a phase 2 study using single-agent panitumumab in combination with radiation therapy in patients with RAS wild-type locally advanced rectal cancer...
November 15, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28853050/clinical-pharmacokinetics-and-pharmacodynamics-of-the-epidermal-growth-factor-receptor-inhibitor-panitumumab-in-the-treatment-of-colorectal-cancer
#20
REVIEW
Sander Ketzer, Kirsten Schimmel, Miriam Koopman, Henk-Jan Guchelaar
Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mCRC. Panitumumab is used in different lines of therapy in combination with chemotherapy, and as monotherapy for the treatment of wild-type (WT) RAS mCRC. It is administered as an intravenous infusion of 6 mg/kg every 2 weeks and has a t ½ of approximately 7...
August 29, 2017: Clinical Pharmacokinetics
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