Help
Subscribe


GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy

 24 May 2018

Advanced search
GastroHep.com - the global online resource for all aspects of gastroenterology, hepatology and endoscopy Profile of Roy Pounder

Home

News  
Journals
Review Articles
Slide Atlas
Video Clips
Online Books
Advanced Digestive Endoscopy
Classical Cases
Conference Diary
PubMed
International GH Links
USA GH Links
National GH Links
National GI Societies
Other Useful Links




Emails on Gastroenterology and Hepatology
the National AIDS Treatment Advocacy Project
Visit the gastroenterology section of the EUMS

News

Cetuximab monotherapy or in combination with irinotecan for treatment of irinotecan-refractory metastatic colorectal cancer

Reporting in the latest issue of the New England Journal of Medicine, researchers have tested the efficacy of the monoclonal antibody cetuximab, either alone or in combination with a first line therapy, as a treatment in metastatic colorectal cancer.

News image

fiogf49gjkf04

Irinotecan is a first-line treatment for colorectal cancer that, along with other therapies, has helped increase the median survival among colorectal cancer patients from 12 months to about 18 to 21 months over the 10 years.

However, some patients do not respond to treatment with irinotecan and so other therapies are required for such patients.

A research team from hospitals across Europe has therefore investigated the use of cetuximab, a monoclonal antibody that binds with high specificity to the epidermal growth factor receptor (EGFR).

This receptor is of relevance in colorectal cancer because in up to 80% of patients with colorectal cancer, there is up-regulation and expression of the EGFR gene. Furthermore, expression of the gene has been shown to be associated with poor survival.

Through binding of its ligand (epidermal growth factor, or transforming growth factor-) EGFR is involved in signaling pathways that become deregulated in cancer cells, including cell differentiation, proliferation, migration, angiogenesis and apoptosis.

Cetuximab has clinically significant activity in patients with irinotecan-refractory colorectal cancer
New England Journal of Medicine

By binding to EGFR, cetuximab blocks activation of these signaling pathways, thus helping to control the cancerous activities of the cells on which EGFR is expressed. In addition, cetuximab has also been shown in experimental systems to enhance the effects of irinotecan and radiotherapy.

Led by Dr David Cunningham, from the Royal Marsden Hospital, in Surrey, England, the research team compared the efficacy of cetuximab alone with that of cetuximab in combination with irinotecan in patients with metastatic colorectal cancer that was refractory to treatment with irinotecan.

329 patients whose disease had progressed during or within 3 months after treatment with an irinotecan-based regimen were randomly assigned to receive either cetuximab and irinotecan (218 patients) or cetuximab monotherapy (111 patients).

Cetuximab was administered at an initial dose of 400 mg/m2, followed by weekly infusions of 250 mg/m2, while patients receiving the combination therapy received their irinotecan at the same dose and schedule as that given during their most recent prestudy therapy.

In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted.

Tumor response was evaluated every 6 weeks for the first 24 weeks and then at 3 month intervals, using either CT or MRI scans.

Each patient was evaluated radiologically for tumor response and was also evaluated for the time to tumor progression, survival and side-effects of treatment.

Patients receiving the combination therapy were found to respond at a significantly higher rate than those in the monotherapy cohort (22.9% compared to 10.8%).

The median time to progression was also significantly greater in the combination therapy group (4.1 compared to 1.5 months in the monotherapy group).

The median survival time was 8.6 months in the combination therapy group and 6.9 months in the monotherapy group.

However, toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone.

Commenting on their findings, Dr Cunningham said that the observed tumor-response rate of 22.9% in the combination therapy group was clinically important, since after the standard drugs (including irinotecan) have failed, there are no accepted treatment options.

"Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer," he concluded.

N Engl J Med 2004; 351 (4): 337 - 345
23 July 2004

Go to top of page Email this page Email this page to a colleague

 24 May 2018 
Patient-reported outcome measures in IBD trials
 24 May 2018 
Alcohol consumption and outcomes in drug-induced liver injury
 24 May 2018 
Precision medicine for tumors
 23 May 2018 
Management of perianal fistulas in Crohn’s disease
 23 May 2018 
Cardiovascular risk in diabetes mellitus with NAFLD
 23 May 2018 
High body mass index is and ulcerative colitis
 22 May 2018 
Worldwide H.pylori prevalence
 22 May 2018 
PPI and risk of stroke
 22 May 2018 
Online tool predicts bowel dysfunction severity prior to anterior resection
 21 May 2018 
Depressive symptoms in IBD youth
 21 May 2018 
PPI use and cognitive decline
 21 May 2018 
Fecal incontinence and quality of life in IBD
 18 May 2018 
Esophageal dilatation in clinical practice 
 17 May 2018 
IBD and later extraintestinal manifestations
 17 May 2018 
Repeat stool DNA testing
 17 May 2018 
IBS and chronic fatigue following GI infection
 16 May 2018 
Factors associated with fecal incontinence
 16 May 2018 
Diagnostic delay in Crohn's disease
 16 May 2018 
Cardiovascular risk in diabetes mellitus with NAFLD
 15 May 2018 
Guidelines for management of Crohn's
 15 May 2018 
Hep B in the Grey Zone
 15 May 2018 
New therapies for CDI
 14 May 2018 
Blood test for the diagnosis of fibrotic NASH
 14 May 2018 
Outcomes at bariatric centers of excellence
 14 May 2018 
Management of perianal fistulas in Crohn’s
 11 May 2018 
Detection of undiagnosed celiac disease
 11 May 2018 
Alcohol consumption and drug-induced liver injury
 10 May 2018 
Post‐operative complications in elderly IBD
 10 May 2018 
Colorectal cancer screening
 10 May 2018 
Fibrosis in patients with chronic hepatitis B
 09 May 2018 
Fecal incontinence
 09 May 2018 
Health problems and IBS
 09 May 2018 
Esophageal dilatation in clinical practice 
 07 May 2018 
Omitting antibiotics in uncomplicated acute diverticulitis
 07 May 2018 
Health problems and IBS
 07 May 2018 
Assessment of diminutive colorectal polyps
 04 May 2018 
National Institutes of Health workshop and obesity
 04 May 2018 
Factors associated with fecal incontinence
 04 May 2018 
Colorectal cancer screening and ethnic inequities
 03 May 2018 
Gastrointestinal ultrasound in IBD
 03 May 2018 
Ultransonography in postsurgical recurrence in Crohn's
 02 May 2018 
Symptom assessment in cirrhotic ascites
 02 May 2018 
Hep C antiviral treatment and liver cancer risk
 02 May 2018 
Chronic Hep B
 01 May 2018 
European guidelines on pancreatic cystic neoplasms
 01 May 2018 
Interferon‐free regimens in Hep C
 01 May 2018 
Age at IBD onset and extraintestinal complications
 30 April 2018 
Formula for preterm infants
 30 April 2018 
Primary antibiotic resistance and sequential therapy for H. pylori
 27 April 2018 
Eastern and western practices for endoscopic resection of colorectal lesions
 27 April 2018 
Anxiety scale for chronic esophageal disease
 27 April 2018 
Disease activity in eosinophilic esophagitis
 26 April 2018 
Obesity and physical activity in diverticulosis
 26 April 2018 
Primary sclerosing cholangitis in the USA
 25 April 2018 
Aspirin and pancreatic cancer
 25 April 2018 
Central mediators of irinotecan-induced steatohepatitis
 25 April 2018 
Neuroimaging in Hep C
 24 April 2018 
Scoring system identifies cancer risk in Barrett's
 24 April 2018 
Microbiome in athletes vs sedentary subjects
 23 April 2018 
Genome-wide study on HBV-related acute-on-chronic liver failure

Blackwell Publishing


GastroHep.com is a Blackwell Publishing registered trademark
© 2018 Wiley-Blackwell and GastroHep.com and contributors
Privacy Statement
Disclaimer
About Us