Cerrahi Sonrasi Tedavi Secenekleri...

Adjuvant therapy for pancreatic ductal adenocarcinoma (treatment given after resection) improves both median and long-term survival. In the past decade, gemcitabine in combination with 5-fluorouracil (5-FU) based chemoradiotherapy has become the adjuvant treatment of choice. This regimen has been shown to improve median and long-term survival when compared with surgery alone in the largest trial of resected patients in North America (RTOG 97-04). In contrast, the largest European trial has shown no benefit to the chemoradiotherapy (ESPAC-1), and thus in Europe, adjuvant treatment tends to utilize chemotherapy alone. The focus in recent years has been to study combination therapies by adding other cytotoxic agents—such as capecitabine, cisplatin, or mitomycin-C—to a gemcitabine-based regimen, or by combining gemcitabine with newer molecular targeted therapies that affect specific cellular pathways, such as topoisomerase-1 inhibitors, matrix metalloproteinase inhibitors, vascular endothelial growth factor inhibitors, or epidermal growth factor inhibitors. To date, the majority of these trials have shown limited clinical efficacy with drug combinations, except for the epidermal growth factor receptor (EGFR) inhibitor erlotinib, which has shown a modest survival benefit.

With the recent mapping of the pancreatic genome, more attention is being drawn to the specific genetic alterations and major signaling pathways underlying pancreatic ductal adenocarcinoma. This may allow for the accelerated identification and development of specific targeted agents. The newest trials under development include the use of specific targeted agents such as insulin-like growth factor 1–receptor inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and c-Met inhibition, as well as the use of immunotherapy for the adjuvant treatment of pancreatic ductal adenocarcinoma. Many laboratories are currently working on better defining the crucial intracellular signaling pathways that are abnormal in pancreatic and other periampullary adenocarcinomas, with the focus on defining a therapeutic target specific for each resected tumor. Given the complex nature of genetic alterations in pancreatic ductal adenocarcinoma, such a personalized treatment model may be critical to developing more effective adjuvant treatment strategies.