One group at particularly high risk of developing pancreatic cancer are those with pancreatic cysts called intraductal papillary mucinous neoplasms (IPMNs). These cysts are often precursors to malignant tumors, and even those who undergo partial pancreatectomy to have them removed face an increased risk of developing cancer in the pancreatic remnant. Approximately 25% will develop radiographic signs of IPMN progression within three to four years of resection.
Hoping to improve the odds, a multi-institutional team of doctors is investigating whether an anti-inflammatory drug regimen could stop or slow the progression from IPMN to pancreatic cancer.
What Is Chemoprevention?
Chemoprevention is an approach being explored in several cancers, such as the use of the estrogen-blocking pill tamoxifen by women at high risk of developing breast cancer. But this is the first chemoprevention trial for pancreatic adenocarcinoma.
The drug used in the IPMN trial is sulindac, a nonsteroidal anti-inflammatory drug (NSAID) that works by blocking cyclooxygenase-2 (COX-2), an enzyme that increases pain and inflammation. COX inhibitors have been shown to be effective in reducing inflammation.
“We know from 10 years of research that patients develop significant inflammation as their disease progresses, and we believe this inflammation may be a driver of pancreatic cancer,” says one of the trial’s lead investigators, Peter Allen, M.D., Chief of the Division of Surgical Oncology at Duke University School of Medicine, Durham, North Carolina. Allen has teamed up with doctors from Johns Hopkins Medicine (Baltimore, Maryland), Massachusetts General Hospital (Boston, Massachusetts), and Memorial Sloan Kettering Cancer Center (New York) to test the treatment on 200 IPMN patients.
Half of the participants will be given sulindac (200 mg by mouth twice daily), and the other half will receive a placebo. They will be closely monitored for three years, with alternating CT imaging and endoscopic ultrasound/fluid aspiration every six months.
The primary endpoint of the National Cancer Institute-funded phase II trial will be the rate of radiographic progression after three years. The team will also assess the effects of the treatment on cyst fluid inflammatory markers and test the use of radiographic assessment (radiomics) for early detection of progression to malignancy.
“We are excited to see if reducing this inflammation can slow progression of the disease,” Allen says.