Phase I study of the anti-heparin-binding epidermal growth factor-like growth factor antibody U3-1565 with cetuximab in patients with cetuximab- or panitumumab-resistant metastatic colorectal cancer

SummaryKRAS wild-type colorectal cancers initially responsive to anti-endothelial growth factor receptor (EGFR) antibodies [cetuximab (Cetu)/panitumumab (Pani)] develop acquired resistance. Overexpression of EGFR ligands such as heparin-binding EGF-like growth factor (HB-EGF) may be one resistance mechanism. This phase I study of U3-1565, anti-HB-EGF antibody, and Cetu combination therapy enrolled patients withKRAS wild-type metastatic colorectal cancer who had received two ≤ regimens with fluoropyrimidine, oxaliplatin, irinotecan, and Cetu/Pani and had disease progression on Cetu/Pani. Recommended dose (RD) was determined in the 1st stage, followed by evaluation of efficacy at the RD level in the 2nd-stage. Cetu was given at a loading dose of 400 mg/m2 followed by weekly infusions of 250  mg/m2 in levels 1 and 0. U3-1565 was administered at a loading dose of 24  mg/m2 followed by biweekly infusions of 16  mg/m2 in level 1 and 16 –12 mg/m2 in level 0. Twenty-two patients were enrolled. No dose-limiting toxicities were observed among three patients in level 1 in the first stage, which was determined as RD. Grade 3 or higher adverse events occurred in 59.1%; those in ≥5% of patients were anemia, γ-GTP elevation, and acneiform rash. Overall response rate was 0.0% [95% confidence interval (CI): 0.0%–15.4%] and disease control was achieved in 17 patients (77.3%, 95% CI: 54.6%–92.2%). Median progression-free survival time was 8...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Conclusions: The use of pbt, but not preoperative anemia, was independently associated with worse overall and recurrence-free survival in nonmetastatic colorectal cancer. For better oncologic outcomes, our findings indicate a need to reduce the use of blood transfusion during the perioperative period. PMID: 31285680 [PubMed - in process]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
JTZ-951 (enarodustat), a hypoxia-inducibe factor prolyl hydroxylase inhibitor, stabilizes HIF-α protein and induces erythropoiesis without effects on the function of vascular endothelial growth factor. Eur J Pharmacol. 2019 Jul 10;:172532 Authors: Fukui K, Shinozaki Y, Kobayashi H, Deai K, Yoshiuchi H, Matsui T, Matsuo A, Matsushita M, Tanaka T, Nangaku M Abstract JTZ-951 (enarodustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor. JTZ-951 has inhibitory activities on human HIF-prolyl hydroxylase 1-3, but not on various receptors or enzymes. In Hep3B cells, JTZ-951 incre...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Listen to critics of the Wheat Belly lifestyle and you’d think that, by banishing all things wheat and grains from your life, you will be excommunicated from your church, tossed out of your club, ostracized by friends and family, and suffer dire health consequences like heart disease and colon cancer. After all, they say that you are eliminating an entire food group and will be crippled by lack of fiber and nutrients. Worse, our focus on increasing our intake of fats and oils will get you a heart attack, three stents, or bypass surgery and you’ll be obliged to take Lipitor and Repatha for a lifetime. First of a...
Source: Wheat Belly Blog - Category: Cardiology Authors: Tags: Wheat Belly Lifestyle grain-free Weight Loss Source Type: blogs
Condition:   Colorectal Cancer Intervention:   Diagnostic Test: Colonoscopy, gastroscopy, virtual colonoscopy, CT scan Sponsor:   Wirral University Teaching Hospital NHS Trust Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
BACKGROUND: There is still controversy about the relationship between preoperative anemia and outcomes after rectal cancer surgery. OBJECTIVE: The aim of this study was to analyze the association between preoperative anemia and postoperative complications and the survival of patients undergoing surgery for rectal cancer in the era of laparoscopic surgery and modern perioperative care. DESIGN: This was a cohort study. SETTINGS: Data were gathered from 71 hospitals in The Netherlands. PATIENTS: Patients who underwent resection for rectal cancer in 2011, for whom preoperative hemoglobin level was registered, wer...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contribution: Colorectal Cancer Source Type: research
ConclusionThis is one of the largest studies to date to describe the epidemiology of EoCRC in USA. We found EoCRC to occur predominantly in the Caucasian and female population. EoCRC presented more frequently with left-sided and rectal CRC. We also identified signs/symptoms as well as comorbidities associated with EoCRC. Patients with these features may benefit from earlier screening.
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
AbstractBackgroundTo assess the impact of primary tumor resection (PTR) on survival and morbidity in incurable colorectal cancer.MethodsSystematic literature review and meta-analysis to compare PTR versus primary tumor intact (PTI).ResultsSeventy-seven studies were included, reporting on 159,991 participants (94,745 PTR; 65,246 PTI). PTR improved overall survival (hazard ratio [HR] 0.59,P 
Source: World Journal of Surgery - Category: Surgery Source Type: research
Colorectal cancer (CRC) is common, affecting>40,000 people a year in the UK. Most cancers are sporadic but a few, such as those occurring at a younger age, have a clear genetic basis. Most are situated in the rectum or rectosigmoid and cause rectal bleeding, often with a looser or more frequent stool. Right-sided cancers typically result in anaemia, because the blood in the stool is occult and unnoticed by the patient. Almost all symptoms of malignancy can also be caused by benign disease. Diagnosis relies on luminal imaging, with colonoscopy being the gold standard.
Source: Medicine - Category: Internal Medicine Authors: Tags: Colorectal cancer Source Type: research
Authors: Kasumi E, Sato N Abstract Peritoneal dissemination describes a state where tumor cells spread to the surface of the peritoneum and become engrafted. Peritoneal dissemination reduces the quality of life and prognosis of cancer patients. Currently, there are few effective therapies or preventative treatments for peritoneal dissemination. The aim of this study was to evaluate a ketogenic diet, characterized by high fat, moderate protein and low carbohydrate content, as a novel therapy in a mouse model of peritoneal dissemination. BALB/c mice were intraperitoneally inoculated with colon 26, a murine colon aden...
Source: Journal of Clinical Biochemistry and Nutrition - Category: Nutrition Tags: J Clin Biochem Nutr Source Type: research
217Objectives: The standardized uptake value (SUV) of physiologic F-18 fluorodeoxyglucose (FDG) liver uptake sometimes varies greatly from individual to individual, in the absence of obvious pathology in the liver. Previous studies have reported that body weight (BW) and body mass index (BMI) were significant factors associated with physiologic FDG uptake of the liver. On the other hands, the clinical significance of increased or decreased liver uptake on FDG-positron emission tomography (PET) is not well understood. In daily clinical practice, reduction of physiologic FDG uptake in the liver is sometimes identified on FDG...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: GI & amp;acirc; amp;euro; ' Colorectal, Liver, Esophageal Source Type: research
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