Adjuvant Chemoradiation for Pancreatic Cancer: Past, Present and Future

Adjuvant chemoradiation began to be investigated for pancreatic cancer over three decades ago. During the intervening years we have achieved a better understanding of the molecular and genetic basis of pancreatic cancer; however the survival of patients treated with the best modern therapies has changed very little. According to data from the American Cancer Society, the 5-year survival for pancreatic cancer patients remains a dismal 5%, up from a historical 3% three decades ago (1). In 2007, an estimated 37,170 newly diagnosed cases of pancreatic cancer in the United States will be nearly equaled by an estimated 33,170 pancreatic cancer deaths (1). This underscores the continued need to develop novel multimodality treatment approaches to this disease. Surgery remains the cornerstone to any hope for long-term survival, however only approximately 10–20% of newly diagnosed patients present with nonmetastatic and potentially resectable disease (2). Pancreatic cancer is considered uniformly fatal in patients unable to undergo a resection. With respect to the minority of patients with resectable disease, cooperative groups both in the United States (US) and Europe have conducted randomized clinical trials in recent decades that have sought to define the potential benefit of adjuvant chemotherapy or adjuvant chemoradiotherapy versus surgery alone for patients with resectable disease. The results of these trials have been conflicting and as a consequence, no current standard exists with respect to adjuvant therapy. Gemcitabine appears to be the most promising agent based on recent phase III trials and may provide a foundation on which to build future trial designs (3, 4). Refinements in delivery techniques for continuous-course modern radiation therapy (RT) as well as promising targeted therapies may also improve upon historical outcomes when added to a gemcitabine backbone. The ideal time sequence of combined adjuvant therapies is also an area of active deliberation. Though there is no current standard for adjuvant therapy in pancreatic cancer, continued investigations into combinations of chemotherapy, radiation therapy, and biologic therapy are warranted. This chapter reviews the historical trials that have defined the potential benefits for adjuvant chemoradiation and examine ongoing and future trial concepts for adjuvant chemoradiation.