Adjuvant Chemotherapy after Surgery for Pancreatic Cancer

Chemoradiotherapy using fluorouracil was initially investigated as a postoperative adjuvant therapy for pancreatic cancer. However, a large randomized controlled trial (RCT) of surgery, chemoradiotherapy, and chemotherapy demonstrated that chemoradiotherapy was inferior to no chemoradiotherapy, while the efficacy of radiotherapy as adjuvant therapy was controversial. Since gemcitabine was established as a standard therapy for unresectable pancreatic cancer, several RCTs have revealed that gemcitabine is also an effective adjuvant therapy. In Japan, S-1, an oral fluoropyrimidine, was approved for the treatment of pancreatic cancer, and a phase III study compared S-1 with gemcitabine as adjuvant therapy. This study examined whether S-1 was non-inferior to gemcitabine and found it superior. As a result, S-1 is recognized as the first-choice adjuvant therapy for pancreatic cancer in Japan. FOLFIRINOX or gemcitabine plus nab-paclitaxel was recently demonstrated to prolong survival in patients with metastatic pancreatic cancer. To improve the survival rate of patients who undergo surgery, these chemotherapeutic regimens with higher response rate are also currently under investigation compared with gemcitabine as adjuvant therapies in RCTs. Furthermore, neoadjuvant therapy using gemcitabine plus S-1, FOLFIRINOX, or gemcitabine plus nab-paclitaxel is expected to improve outcomes of surgical treatments, and various clinical trials of neoadjuvant therapies using those regimens are currently under investigation.