Selecting chemotherapy for pancreatic cancer: Far away or so close?

Pancreatic cancer is a lethal disease with a very poor prognosis. In contrast to treatments for many other tumor types, cytotoxic agents are still the first-line drugs for pancreatic cancer in both the palliative and adjuvant settings. Some progress has been made in recent years, but most large phase 3 studies have not shown significant improvements in survival. Because the available drugs and regimens are limited in both type and effect, the selection of chemotherapy based on clinicopathologic characteristics may be consequential for pancreatic cancer. In the present report, we focused on 7 landmark clinical trials for pancreatic cancer. We observed that FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) and NG (nab-paclitaxel and gemcitabine), 2 first-line regimens, exerted opposite effects on metastatic pancreatic cancer patients with different baseline carbohydrate antigen 19-9 (CA19-9) levels. This suggested that not only the performance status but possibly also CA19-9 levels should be considered when making a therapeutic choice for patients with advanced pancreatic cancer. Moreover, we found that patients with a diagnosis of pancreatic cancer who have undergone a surgical resection with a negative margin (R0) may benefit more from fluorouracil and/or oral prodrugs of fluorouracil-based adjuvant therapy than from gemcitabine. Conversely, gemcitabine or gemcitabine-based regimens may be more effective for patients with a positive resection margin (R1). Based on these findings, we propose flowcharts for selecting chemotherapy for both advanced and resected pancreatic cancer. Furthermore, we present possible mechanisms and interpretations underlying the selection of chemotherapy for pancreatic cancer and propose the tumor burden as a key variable in this process. Regardless of the possible bias and exact treatment selection process, this study offers an opportunity to improve patient outcomes by using agents currently used in the therapy of pancreatic cancer. Although these conclusions are based on indirect evidence, we provide insights and possibilities to drive the selection of chemotherapy for pancreatic cancer.