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Panitumumab

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https://www.readbyqxmd.com/read/29326440/braf-inhibition-upregulates-a-variety-of-receptor-tyrosine-kinases-and-their-downstream-effector-gab2-in-colorectal-cancer-cell-lines
#1
Ricarda Herr, Sebastian Halbach, Miriam Heizmann, Hauke Busch, Melanie Boerries, Tilman Brummer
BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single agents. This unresponsiveness was mechanistically attributed to the loss of negative feedbacks on the epidermal growth factor receptor (EGFR) and initiated clinical trials that combine BRAF (and MEK) inhibitors, either singly or in combination, with the anti-EGFR antibodies cetuximab or panitumumab...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29323221/chemotherapy-plus-panitumumab-versus-chemotherapy-plus-bevacizumab-in-metastatic-colorectal-cancer-a-meta-analysis
#2
Zhigui Li, Yuqian Huang, Rui Zhao, Yaping Cui, Yong Zhou, Xiaoting Wu
Panitumumab and bevacizumab have been widely used in combination with chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC). Whether panitumumab or bevacizumab was the optimal option remained controversial. Thus, we conducted a meta-anaylsis to evaluate chemotherapy plus panitumumab (C + P) versus chemotherapy plus bevacizumab (C + B) in wild type RAS mCRC. Electronic databases including PubMed, Embase, and Web of Science, Cochrane Library, ClinicalTrials.gov, were searched...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29314858/panitumumab-modified-with-metal-chelating-polymers-mcp-complexed-to-111in-and-177lu-an-egfr-targeted-theranostic-for-pancreatic-cancer
#3
Sadaf Aghevlian, Yijie Lu, Mitchell A Winnik, David W Hedley, Raymond M Reilly
A metal-chelating polymer (MCP) with a polyglutamide (PGlu) backbone presenting on average 13 DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators for complexing 111In or 177Lu and 10 polyethylene glycol (PEG) chains to minimize liver and spleen uptake was conjugated to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), panitumumab. Since panitumumab-MCP may be dual-labeled with 111In and 177Lu for SPECT, or radioimmunotherapy (RIT) exploiting the Auger electrons or β-particle emissions, respectively, we propose that panitumumab-MCP could be a useful theranostic agent EGFR-positive PnCa...
January 9, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29314360/patient-reported-symptoms-and-stepwise-symptom-management-in-patients-on-epidermal-growth-factor-inhibitors-a-retrospective-descriptive-cohort-study
#4
J J Koldenhof, M H G Langenberg, P O Witteveen, S C C M Teunissen
Adverse events (AEs) of epidermal growth factor inhibitors (EGFRi) influence well-being with a risk to dose modifications (DMs). Hereby, clinical benefit of treatment might be affected. This retrospective cohort study was set up to gain insight into the suitability and added value of a patient-reported outcome measurement tool (PROM), together with a stepwise intervention management plan for EGFRi-related AEs in daily practice. The primary objective was to gain insight into total treatment duration and DMs, and the secondary objective to gain insight into patient-reported symptoms and well-being as well as healthcare professional-reported AEs...
January 4, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29311468/-economic-evaluation-of-mfolfox6-based-first-line-regimens-for-unresectable-advanced-or-recurrent-colorectal-cancer-using-clinical-decision-analysis
#5
Toshihiro Shida, Yuji Endo, Tadashi Shiraishi, Takashi Yoshioka, Kaoru Suzuki, Yuka Kobayashi, Yuki Ono, Toshinori Ito, Tadao Inoue
 We evaluated four representative chemotherapy regimens for unresectable advanced or recurrent KRAS-wild type colorectal cancer: mFOLFOX6, mFOLFOX6+bevacizumab (Bmab), cetuximab (Cmab), or panitumumab (Pmab). We employed a decision analysis method in combination with clinical and economic evidence. The health outcomes of the regimens were analyzed on the basis of overall and progression-free survival. The data were drawn from the literature on randomized controlled clinical trials of the above-mentioned drugs...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29285233/aio-lq-0110-a-randomized-phase-ii-trial-comparing-oral-doxycycline-versus-local-administration-of-erythromycin-as-preemptive-treatment-strategies-of-panitumumab-mediated-skin-toxicity-in-patients-with-metastatic-colorectal-cancer
#6
Melanie Kripp, Nicole Prasnikar, Ursula Vehling-Kaiser, Julia Quidde, Salah-Eddin Al-Batran, Alexander Stein, Kai Neben, Carla Verena Hannig, Hans Werner Tessen, Tanja Trarbach, Axel Hinke, Ralf-Dieter Hofheinz
Background: Dermatologic toxicities, especially akne-like skin rash, are the most common side-effects associated with anti-epidermal growth factor receptor (EGFR) therapy. Preemptive treatment with oral tetracyclines is recommended as a standard. Topical prophylactic options have thus far not been compared to tetracyclines. In the current study, we sought to establish an alternative topical treatment. Patients and methods: In this multicentre, randomized, open-label phase II study patients with (K)Ras-wildtype colorectal cancer receiving panitumumab were randomized (1:1) to receive either doxycycline 100 mg b...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259073/phase-ii-study-of-panitumumab-in-ras-wild-type-metastatic-adenocarcinoma-of-small-bowel-or-ampulla-of-vater
#7
Pat Gulhati, Kanwal Raghav, Rachna Shroff, Gauri Varadhachary, Milind Javle, Wei Qiao, Huamin Wang, Jeffrey Morris, Robert Wolff, Michael J Overman
LESSONS LEARNED: Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted...
December 19, 2017: Oncologist
https://www.readbyqxmd.com/read/29237807/molecularly-targeted-cancer-combination-therapy-with-near-infrared-photoimmunotherapy-and-near-infrared-photo-release-with-duocarmycin-antibody-conjugate
#8
Tadanobu Nagaya, Alexander P Gorka, Roger R Nani, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L Choyke, Martin J Schnermann, Hisataka Kobayashi
Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). However, the effect of NIR-PIT can be enhanced when combined with other therapies. NIR photocaging groups, based on the heptamethine cyanine scaffold, have been developed to release bioactive molecules near targets after exposure to light. Here, we investigated the combination of NIR-PIT employing panitumumab-IR700 (pan-IR700) and the NIR-releasing compound, CyEt-Panitumumab-Duocarmycin (CyEt-Pan-Duo)...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29204427/natural-killer-cells-activity-in-a-metastatic-colorectal-cancer-patient-with-complete-and-long-lasting-response-to-therapy
#9
Alessandro Ottaiano, Maria Napolitano, Monica Capozzi, Salvatore Tafuto, Antonio Avallone, Stefania Scala
Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA...
November 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29187286/inflammation-of-actinic-keratosis-during-panitumumab-therapy
#10
M M Escudero-Góngora, L J Del Pozo-Hernando, O Corral-Magaña, E Antón
No abstract text is available yet for this article.
November 26, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29183279/panitumumab-use-in-metastatic-colorectal-cancer-and-patterns-of-ras-testing-results-from-a-europe-wide-physician-survey-and-medical-records-review
#11
J Han van Krieken, George Kafatos, James Bennett, Laurent Mineur, Jiří Tomášek, Etienne Rouleau, Pavel Fabian, Giovanna De Maglio, Pilar García-Alfonso, Giuseppe Aprile, Parijan Parkar, Gerald Downey, Gaston Demonty, Jörg Trojan
BACKGROUND: In Europe, treatment of metastatic colorectal cancer (mCRC) with panitumumab requires prior confirmation of RAS wild-type mutation status. Two studies - a physician survey and a medical records review (MRR) - were conducted to evaluate the use of panitumumab and awareness among prescribing oncologists of the associated RAS testing requirements in clinical practice. METHODS: Both studies enrolled participants from nine European countries and were carried out in three consecutive rounds...
November 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29170802/pharmacokinetics-and-safety-of-panitumumab-in-a-patient-with-chronic-kidney-disease
#12
L L Krens, J M Baas, H J Guchelaar, H Gelderblom
PURPOSE: Data on panitumumab dosing in cancer patients with renal insufficiency are lacking. Here, we report a 63-year-old metastatic colorectal cancer patient with chronic kidney injury with a glomerular filtration rate of approximately 11 mL/min. METHODS: Pharmacokinetic parameters, including dose-normalized area under the curve, clearance and elimination half-life (T 1/2) after the 11th and 12th infusions were estimated using trapezoidal non-compartmental methods...
November 23, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29169974/a-prospective-multicenter-phase-ii-study-of-the-efficacy-and-feasibility-of-15-minute-panitumumab-infusion-plus-irinotecan-for-oxaliplatin-and-irinotecan-refractory-kras-wild-type-metastatic-colorectal-cancer-short-infusion-of-panitumumab-trial
#13
Kohei Akiyoshi, Tetsuya Hamaguchi, Kenichi Yoshimura, Naoki Takahashi, Yoshitaka Honma, Satoru Iwasa, Atsuo Takashima, Ken Kato, Yasuhide Yamada, Hisashi Onodera, Shigeyuki Takeshita, Hisateru Yasui, Gen Sakai, Sotaro Akatsuka, Kohei Ogawa, Yosuke Horita, Yushi Nagai, Yasuhiro Shimada
BACKGROUND: In some recently updated clinical guidelines, the fully humanized monoclonal antibody panitumumab, combined with irinotecan, has been recommended as an optional third-line chemotherapy for KRAS wild-type metastatic colorectal cancer (mCRC). The present prospective, multicenter phase II study evaluated the effectiveness and safety of short 15-minute panitumumab infusions. PATIENTS AND METHODS: From January 2011 to December 2011, patients with KRAS wild-type mCRC were enrolled at 8 centers...
October 16, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29158469/molecular-basis-for-necitumumab-inhibition-of-egfr-variants-associated-with-acquired-cetuximab-resistance
#14
Atrish Bagchi, Jaafar N Haidar, Scott W Eastman, Michal Vieth, Michael Topper, Michelle D Iacolina, Jason M Walker, Amelie Forest, Yang Shen, Ruslan D Novosiadly, Kathryn M Ferguson
Acquired resistance to cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR), impacts clinical benefit in head and neck, and colorectal cancers (CRC). One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab resistance substitution, S468R (or S492R, depending on the amino acid numbering system)...
November 20, 2017: Molecular Cancer Therapeutics
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
#15
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-photoabsorber 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 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29101848/human-fc-receptor-like-5-distinguishes-igg2-disulfide-isoforms-and-deamidated-charge-variants
#16
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
#17
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
#18
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
#19
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
#20
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
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