Treatment for locally advanced disease

Abstract

Most patients ( pts) with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy (CT) alone in Japan. Chemoradiotherapy (CRT) is also a treatment option, but the role of radiotherapy (RT) remains controversial. Recently, induction CT followed by CRT is recognized as one potentially promising strategy. Retrospective analysis of GERCOR phase II and III studies demonstrated significantly better progression‐free survival (PFS) and overall survival (OS) in pts without tumor progression during 3 months of initial CT who were subsequently treated with CRT compared to continuing CT alone. The GERCOR LAP07 phase III study did not show a survival benefit with CRT compared to CT alone in pts with controlled disease after 4 months of induction CT, but there was a trend towards improved PFS, a significant local control benefit, and a significantly prolonged treatment‐free interval in the CRT arm. In Japan, randomized phase II study was conducted to evaluate the efficacy and safety of CRT with and without induction CT (JCOG1106). Histologically proven LAPC pts were randomized to CRT (Arm A) or induction CT followed by CRT (Arm B). Pts in Arm A received RT with concurrent S‐1. Pts in Arm B received induction gemcitabine (GEM) for 12 weeks, and then, only pts with controlled disease received same CRT as Arm A. After CRT, GEM was continued until disease progression or unacceptable toxicity in both arms. Primary endpoint was OS. The results of JCOG1106 study are planned to be presented at the 2015 ASCO annual meeting. On the other hand, FOLFIRINOX and GEM/nab‐paclitaxel were reported to improve survival compared to GEM alone in the metastatic setting, and, despite the lack of enough evidence from prospective trials, these regimens are also being increasingly used in the management of LAPC. JCOG is also conducting a randomized phase II study of FOLFIRINOX vs. GEM/nab‐paclitaxel to select more promising CT regimen for subsequent phase III study comparing with CRT.