Therapy for regionally unresectable pancreatic cancer.

Chemoradiotherapy for unresectable LAPA is associated with a median survival time of 9 months or more and manageable toxic side effects. Experience with RT-FSP provides evidence that chemoradiotherapy may extend survival time with or without resection. Chemoradiotherapy or entry into clinical trials is the standard for LAPA. The next generation of clinical trials for LAPA will incorporate newer agents, such as gemcitabine and irinotecan into chemoradiotherapy regimens. Novel agents, such as matrix-metaloproteinase inhibitors, transcription factor inhibitors, antiangiogenic factors, cyclooxegenase-2 inhibitors, and agents that target the K-ras point mutations associated with 90% of pancreatic cancers, are in early phases or clinical development and may have activity for micrometastic or minimal residual disease. Lower toxicity makes these drugs attractive agents for maintenance therapies. The multitude of new agents provides hope to patients and a welcome challenge for further investigation.