Therapeutic Strategies for Patients with Advanced Small Bowel Adenocarcinoma: Current Knowledge and Perspectives

Small bowel adenocarcinoma (SBA) is diagnosed at an advanced (unresectable or metastatic) tumor stage in approximately one-third of cases. This is partly due to the non-specific symptomatol-ogy and limitations in endoscopic and radiologic detection methods. In this context, the prognosis remains poor and systemic chemotherapy appears to benefit patients when compared to best sup-portive care alone, despite the absence of randomized controlled trials. The results of a recent large prospective cohort (ARCAD-NADEGE) reported that the absence of chemotherapy was a predictive factor for a lower overall survival (OS) even though poor differentiation and SBA associated with Crohn’s disease correlate with poor prognosis. In retrospective series, the median OS ranges from approximately 9 to 18 months with current treatment approaches. A combination of a fluoropyrim-idine and oxaliplatin (FOLFOX or CAPOX) appears to be the most utilized and effective first-line chemotherapy regimen. Other front-line alternatives are the combination of 5-FU and cisplatin or fluoropyrimidine and irinotecan (FOLFIRI). In second-line, FOLFIRI is an effective option after progression on platinum-based therapy. Taxane-based therapy appears to be an alternative option, but further evaluation in larger series is needed. To a limited extent, the role of surgical resection for metastatic disease appears to be a valid option, though this approach has not been evaluated in prospective clinical studies. Due to the rareness of the disease, inclusion in clinical trials should be prioritized, and there is hope that targeted therapies and immunotherapy may enter the therapeutic arsenal for these patients.