Ampullary adenocarcinoma (AAC) is a rare form of gastrointestinal cancer, accounting for approximately 0.2% to 0.5% of all gastrointestinal cancers and 7% of all periampullary cancers. The five-year overall survival (OS) for AAC ranges between 30% and 70%, with the pancreatobiliary (PB) subtype believed to exhibit the most aggressive biological behavior. To date, no randomized trials have confirmed a survival improvement after adjuvant chemotherapy for AAC.

Recent retrospective studies have demonstrated that only patients with the PB and mixed subtypes benefit from adjuvant therapy, showing improved median overall survival, whereas no benefit was observed for the intestinal subtype. Although there is evidence of survival improvement with adjuvant treatment for AAC based on histopathological subtype, prospective studies are needed to confirm this. Additionally, the PB and mixed subtypes exhibit the worst five-year OS and the most aggressive biological behavior. A phase II study demonstrated that the combination of Capecitabine and Oxaliplatin (CAPOX) is well-tolerated and results in superior response rates and longer OS compared to other regimens in patients with AAC (all subtypes) and duodenal cancer.