S-1 monotherapy or in combination with leucovorin as second-line treatment in gemcitabine-refractory advanced pancreatic cancer: A phase II study.

e15222 Background: Previous studies have revealed that the fluorouracil derivative S-1as first-line treatment can bring survival benefit and good tolerability for patients with unresectable pancreatic cancer (PC). S-1 in combination with leucovorin (LV) revealed a better efficacy when treating patients with metastatic colorectal cancer. In this study, we compared the efficacy and safety of S-1 or S-1 in combination with LV (SL) as the second-line treatment for patients with metastatic PC after failing to gemcitabine treatment. Methods: The study was a randomized, open-label, controlled study. Patients with metastatic PC who failed gemcitabine-based chemotherapy randomly received S-1 at a dose of 80mg/m2/day, orally administered twice a day; or orally administered in combination with LV 25mg/time and S-1 alone for 14 days, followed by 7 days rest, for a 21-day cycle. The primary end point was progression-free survival (PFS). Results: A total of 92 patients were enrolled from March 2010 to May 2013. The median overall survival (OS) of 47 cases in the S-1 arm was 5.5 months, and median PFS was 1.9 months. In the SL arm, the median OS of 45 cases was 6.3 months and median PFS was 3.0 months. There was no significant difference in the OS (p=0.829) and PFS (p=0.860) between the two arms. The overall response rate in the S-1 arm was not significantly different from the SL arm (p=0.503). The rate of adverse events of grade 3-4 in the SL arm was significantly higher than those of the S-1 arm (p=0.011). Conclusions: As compared with S-1, SL did not improve the survival of patients with metastatic PC who had failed gemcitabine treatment. Further evaluation of the overall benefit of SL relative to S-1 is warranted, considering the higher adverse event rate of grade 3-4 observed in the SL group. Clinical trial information: NCT01074996.