ORLANDO — Early findings from the Aspirin Esomeprazole Chemoprevention Trial indicate that therapy with aspirin and esomeprazole is safe and well tolerated for preventing the progression of Barrett's esophagus to adenocarcinoma.
Since the start of the randomized Aspirin Esomeprazole Chemoprevention Trial (AspECT) in September 2005, 1,192 (83%) of the 1,436 patients have remained on their medication, and just 33 adverse events have been reported, said the study's lead investigator Dr. Janusz Jankowski, professor of medicine, Oxford University (England), at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
AspECT is an ambitious, 10-year clinical trial being conducted in the United Kingdom. The investigators are still recruiting to meet their goal of 3,000 patients. The trial's primary aim is to determine whether treatment with the proton pump inhibitor esomeprazole (Nexium, AstraZeneca) and aspirin can stop Barrett's metaplasia from progressing to adenocarcinoma.
The investigators are also trying to determine whether this therapy will prevent or reduce myocardial infarction.
The United Kingdom is fertile ground for such a study, Dr. Jankowski said at the symposium, also sponsored by the AGA Institute, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.
“The U.K. has the highest incidence of esophageal adenocarcinoma in the world—up to four times greater than that of other countries in Europe. Barrett's metaplasia is twice as common in the U.K. as it is in the United States,” he said in an interview.
Being able to show that aspirin “is incredibly well tolerated” is very gratifying, Dr. Jankowski said, because many people were skeptical that it could be done.
“One of the major criticisms of the study when we tried to get it funded in the first place was that people thought we were mad and dangerous, and that we would kill patients with low-dose aspirin. But about 90% of our patients are still on low-dose aspirin and esomeprazole 2 years into the study with hardly any adverse events, showing the drug combination is very well tolerated.”
So far, 12% of patients randomized to 20 mg esomeprazole have required an increase to 40 mg for symptom control, Dr. Jankowski said.
Besides conversion to high-grade dysplasia or cancer, the other primary end point of the study is all-cause mortality.
Additionally, it will look at the pharmacokinetics of aspirin resistance, genetic markers as potential risk factors for esophageal cancer, and quality of life.
The first planned efficacy analysis is scheduled for 2010, a second interim analysis is due in 2012, and the final analysis is due in 2016.
The trial is funded by Cancer Research UK, Oxford University, and AstraZeneca.
Dr. Jankowski disclosed that he is a consultant to and receives research funding from AstraZeneca.
Being able to show that aspirin 'is incredibly well tolerated' is very gratifying because many people were skeptical. DR. JANKOWSKI