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https://www.readbyqxmd.com/read/29769385/phase-ii-study-of-irinotecan-plus-panitumumab-as-second-line-therapy-for-patients-with-advanced-esophageal-adenocarcinoma
#1
Harry Yoon, Anita Choudhary, Ramla Kosozi, Gurvinder Singh Bali, Ali Zaidi, Ajlan Atasoy, Arlene A Forastiere, Michael K Gibson
LESSON LEARNED: Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29755130/restoring-puma-induction-overcomes-kras-mediated-resistance-to-anti-egfr-antibodies-in-colorectal-cancer
#2
Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang
Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29739790/phase-ib-ii-study-of-second-line-therapy-with-panitumumab-irinotecan-and-everolimus-pie-in-kras-wild-type-metastatic-colorectal-cancer
#3
Amanda Townsend, Niall C Tebbutt, Christos S Karapetis, Pamela Cooper, Nimit Singhal, Sue J Yeend, Louise Pirc, Rohit Joshi, Jennifer Elizabeth Hardingham, Timothy Price
PURPOSE: Inhibition of mTOR in addition to EGFR may overcome resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC). This phase Ib/II study evaluated the safety and efficacy of the combination of irinotecan, panitumumab and everolimus. EXPERIMENTAL DESIGN: Patients with KRAS exon 2 WT mCRC following failure of fluoropyrimidine based therapy received IV irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14 day cycle. The primary endpoint of the phase II study was response rate (RR)...
May 8, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29737864/panitumumab-in-the-treatment-of-metastatic-colorectal-cancer-including-wild-type-ras-kras-and-nras-mcrc
#4
Mark McGregor, Timothy J Price
The humanized monoclonal antibody panitumumab, targeted against EGFR, plays an important role in patients with metastatic colorectal cancer. This article reviews the body of evidence for panitumumab which demonstrates significant benefits across multiple lines of therapy in those without an extended RAS mutation. The use of panitumumab with RAS mutations is not beneficial and possibly harmful. Panitumumab is well tolerated with manageable toxicities. The role of panitumumab continues to evolve as understanding of sequencing of therapies grows...
May 8, 2018: Future Oncology
https://www.readbyqxmd.com/read/29725456/application-of-molecular-targeted-therapies-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#5
REVIEW
Paulina Kozakiewicz, Ludmiła Grzybowska-Szatkowska
Despite the development of standard therapies, including surgery, radiotherapy and chemotherapy, survival rates for head and neck squamous cell carcinoma (HNSCC) have not changed significantly over the past three decades. Complete recovery is achieved in <50% of patients. The treatment of advanced HNSCC frequently requires multimodality therapy and involves significant toxicity. The promising, novel treatment option for patients with HNSCC is molecular-targeted therapies. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib), vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or vascular endothelial growth factor receptor (VEGFR) inhibitors (sorafenib, sunitinib and vandetanib) and inhibitors of phosphatidylinositol 3-kinase/serine/threonine-specific protein kinase/mammalian target of rapamycin...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721094/safety-of-panitumumab-irdye800cw-and-cetuximab-irdye800cw-for-fluorescence-guided-surgical-navigation-in-head-and-neck-cancers
#6
Rebecca W Gao, Nutte Teraphongphom, Esther de Boer, Nynke S van den Berg, Vasu Divi, Michael J Kaplan, Nicholas J Oberhelman, Steven S Hong, Elissa Capes, A Dimitrios Colevas, Jason M Warram, Eben L Rosenthal
Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2 , cohort 2 received 25 mg/m2 , and cohort 3 received 62...
2018: Theranostics
https://www.readbyqxmd.com/read/29703606/final-analysis-of-outcomes-and-ras-braf-status-in-a-randomized-phase-3-study-of-panitumumab-and-best-supportive-care-in-chemorefractory-wild-type-kras-metastatic-colorectal-cancer
#7
Tae Won Kim, Anneli Elme, Joon Oh Park, Anghel Adrian Udrea, Sun Young Kim, Joong Bae Ahn, Ricardo Villalobos Valencia, Srinivasan Krishnan, Nebojsa Manojlovic, Xuesong Guan, Catherine Lofton-Day, A Scott Jung, Eduard Vrdoljak
INTRODUCTION: Tumor rat sarcoma gene (RAS) status is a negative predictive biomarker for anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). We analyzed outcomes according to RAS and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutational status, and evaluated early tumor shrinkage (ETS) and depth of response (DpR) for patients with wild type RAS. PATIENTS AND METHODS: Patients with confirmed metastatic colon or rectum adenocarcinoma, wild type Kristen rat sarcoma gene tumor exon 2 status, clinical/radiologic disease progression or toxicity during irinotecan or oxaliplatin treatment, and no previous anti-EGFR therapy were randomized 1:1 to receive best supportive care (BSC) with or without panitumumab (6...
March 21, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29680500/cross-talk-between-egfr-and-il-6-drives-oncogenic-signaling-and-offers-therapeutic-opportunities-in-cancer
#8
Kriti Ray, Beata Ujvari, Venkata Ramana, John Donald
Epidermal growth factor receptor (EGFR) is a known target in cancer therapy and targeting the receptor has proven to be extremely successful in treating cancers that are dependent on EGFR signaling. To that effect, targeted therapies to EGFR such as Cetuximab, Panitumumab-monoclonal antibodies and Gefitinib, Erlotinib-tyrosine kinase inhibitors have had success in therapeutic scenarios. However, the development of resistance to these drugs makes it necessary to combine anti- EGFR therapies with other inhibitors, so that resistance can be overcome by the targeting of alternate signaling pathways...
April 7, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29666669/-egfr-amplification-induces-sensitivity-to-anti-egfr-therapy-in-pancreatic-acinar-cell-carcinoma
#9
Corentin Richard, Julie Niogret, Romain Boidot, Francois Ghiringhelli
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses...
April 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29650838/-two-cases-of-hepatic-encephalopathy-after-chemotherapy-for-metastatic-colorectal-cancer
#10
Tae Matsumura, Shingo Noura, Masaki Hirota, Yuki Ozato, Daiki Marukawa, Takashi Shuto, Arisa Muratsu, Akinobu Yasuyama, Akihiro Takata, Chikato Koga, Chizu Kameda, Masahiro Murakami, Ryohei Kawabata, Junzo Shimizu, Junichi Hasegawa
We reported 2 cases of hepatic encephalopathy after chemotherapy for advanced colorectal cancer. Case 1: A 49-year-old male was diagnosed advanced sigmoid colon cancer with peritoneal dissemination, multiple liver metastasis and multiple osseous metastasis. After resection of primary lesion, we administered mFOLFOX6 plus bevacizumab combination therapy. He was in comatose(Japan coma scale 200)3 days after 2 courses of administration of this regimen. Case 2: A 57-year-old female was diagnosed advanced rectal cancer with multiple huge liver metastasis and multiple osseous metastasis...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29650279/the-best-strategy-for-ras-wild-type-metastatic-colorectal-cancer-patients-in-first-line-treatment-a-classic-and-bayesian-meta-analysis
#11
REVIEW
Domenico Ciliberto, Nicoletta Staropoli, Francesca Caglioti, Silvia Chiellino, Antonella Ierardi, Rossana Ingargiola, Cirino Botta, Mariamena Arbitrio, Pierpaolo Correale, Pierfrancesco Tassone, Pierosandro Tagliaferri
BACKGROUND: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. METHODS: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients...
May 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29629795/mri-detection-of-intratumoral-fat-in-colorectal-liver-metastases-after-preoperative-chemotherapy
#12
Yudai Nakai, Wataru Gonoi, Akifumi Hagiwara, Yujiro Nishioka, Hiroyuki Abe, Junichi Shindoh, Kiyoshi Hasegawa
OBJECTIVE: The objective of this study was to investigate the incidence and clinical significance of intratumoral fat deposition in colorectal liver metastases (CLMs) after preoperative chemotherapy using dual-echo gradient-recalled echo MRI. MATERIALS AND METHODS: Our institutional review board approved this retrospective radiographic study and waived the requirement for informed patient consent. Fifty-nine patients (33 men, 26 women; median age, 62 years old) who underwent preoperative MRI and curative hepatic resection for colorectal liver metastases after chemotherapy were selected...
April 9, 2018: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/29627309/effect-of-primary-tumor-location-on-second-or-later-line-treatment-outcomes-in-patients-with-ras-wild-type-metastatic-colorectal-cancer-and-all-treatment-lines-in-patients-with-ras-mutations-in-four-randomized-panitumumab-studies
#13
Nele Boeckx, Reija Koukakis, Ken Op de Beeck, Christian Rolfo, Guy Van Camp, Salvatore Siena, Josep Tabernero, Jean-Yves Douillard, Thierry André, Marc Peeters
BACKGROUND: The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. PATIENTS AND METHODS: RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials...
March 8, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29599371/usefulness-of-tas-102-as-third-line-chemotherapy-for-metastatic-colorectal-cancer
#14
Hidejiro Kawahara, Takashi Mouri, Kota Ishida, Nori Matsumoto, Tadashi Akiba, Katsuhiko Yanaga
BACKGROUND/AIM: The feasibility and oncological outcomes of treatment with TAS-102, that is recommended as third-line chemotherapy for patients with metastatic colorectal cancer (mCRC), remain unknown. PATIENTS AND METHODS: Between 2013 and 2015, seven patients (five males, two females) with mCRC who were administered TAS-102 as third-line chemotherapy at our Institution were retrospectively studied. During the same period, seven patients with mCRC with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type primary lesions who were administered irinotecan with panitumumab comprised the control group...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29589315/molecular-testing-for-the-treatment-of-advanced-colorectal-cancer-an-overview
#15
Patrick S Lin, Thomas J Semrad
Concurrent with an expansion in the number of agents available for the treatment of advanced CRC, there has been an increase in our understanding of selection biomarkers to optimize the management of patients with this disease. For CRC patients being considered for anti-EGFR therapy, expanded RAS testing is the standard of care to determine the subset of patients who can benefit from cetuximab or panitumumab in conjunction with chemotherapy. A small fraction of patients have HER2 amplification where emerging data suggest treatment with drugs targeting this alteration...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29587749/folfiri-plus-panitumumab-in-the-treatment-of-wild-type-kras-and-wild-type-nras-metastatic-colorectal-cancer
#16
Caglayan Geredeli, Nurgul Yasar
BACKGROUND: The aim of this study was to investigate the efficacy and safety of first-line panitumumab plus folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in patients with wild-type KRAS and wild-type NRAS metastatic colorectal cancer (mCRC). METHODS: Patients with wild-type KRAS and wild-type NRAS mCRC presenting to the medical oncology department of the Okmeydani Training and Research Hospital in Istanbul, Turkey, between April 2014 and January 2018 were enrolled in this study...
March 27, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29572704/prognostic-impact-of-r0-resection-and-targeted-therapy-for-colorectal-cancer-with-synchronous-peritoneal-metastasis
#17
Dai Shida, Takefumi Yoshida, Taro Tanabe, Shunsuke Tsukamoto, Hiroki Ochiai, Yukihide Kanemitsu
BACKGROUND: The National Comprehensive Cancer Network guidelines recommend R0 resection and targeted therapy, a combination of cytotoxic and molecular targeted agents, such as bevacizumab, cetuximab, and panitumumab, for colorectal cancer with synchronous peritoneal metastasis (M1c). While these therapeutic strategies are drawing attention, their efficacy has not been fully examined. METHODS: The study population comprised 248 consecutive M1c patients who were treated at the National Cancer Center Hospital from 1997 to 2013...
March 23, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29572245/a-phase-i-trial-of-the-igf-1r-antibody-ganitumab-amg-479-in-combination-with-everolimus-rad001-and-panitumumab-in-patients-with-advanced-cancer
#18
Gordana Vlahovic, Kellen L Meadows, Ace J Hatch, Jingquan Jia, Andrew B Nixon, Hope E Uronis, Michael A Morse, M Angelica Selim, Jeffrey Crawford, Richard F Riedel, S Yousuf Zafar, Leigh A Howard, Margot O'Neill, Jennifer J Meadows, Sherri T Haley, Christy C Arrowood, Christel Rushing, Herbert Pang, Herbert I Hurwitz
PURPOSE: This study evaluated the maximum tolerated dose or recommended phase II dose (RPTD) and safety and tolerability of the ganitumab and everolimus doublet regimen followed by the ganitumab, everolimus, and panitumumab triplet regimen. MATERIALS AND METHODS: This was a standard 3 + 3 dose escalation trial. Doublet therapy consisted of ganitumab at 12 mg/kg every 2 weeks; doses of everolimus were adjusted according to dose-limiting toxicities (DLTs). Panitumumab at 4...
March 23, 2018: Oncologist
https://www.readbyqxmd.com/read/29549923/use-of-liquid-biopsy-in-monitoring-colorectal-cancer-progression-shows-strong-clinical-correlation
#19
Qiushi Sun, Yuan Liu, Bo Liu, Yingying Liu
BACKGROUND: Patients with colorectal cancer (CRC) who are sensitive to epidermal growth factor antibodies inevitably acquire drug resistance. This study aimed to determine the usefulness of liquid biopsies for prognosis and clinical correlation. MATERIALS AND METHODS: For liquid biopsy tests, we extracted blood from 140 CRC patients with matched tumor samples. Circulating tumor cells (CTCs) and tumor DNA (ctDNA) were extracted before surgery and treatment. Samples were quantified and tested for mutations in KRAS, NRAS and BRAF...
March 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29531837/exploratory-pooled-analysis-evaluating-the-effect-of-sequence-of-biological-therapies-on-overall-survival-in-patients-with-ras-wild-type-metastatic-colorectal-carcinoma
#20
Marc Peeters, Frédéric Forget, Meinolf Karthaus, Manuel Valladares-Ayerbes, Alberto Zaniboni, Gaston Demonty, Xuesong Guan, Fernando Rivera
Background: The aim of this study was to evaluate the optimal sequence of targeted therapies (epidermal growth factor receptor inhibitors (EGFRi) and vascular endothelial growth factor inhibitors (VEGFi)), combined with chemotherapy, in patients with RAS wild-type (WT) metastatic colorectal carcinoma (mCRC). Exploratory analyses of overall survival (OS) for patients treated with either first-line panitumumab (EGFRi) and second-line VEGFi therapy, or first-line bevacizumab (VEGFi) and second-line EGFRi, were conducted...
2018: ESMO Open
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