The addition of leucovorin to S-1 significantly improved progression-free survival compared with S-1 alone in patients with advanced pancreatic cancer who were refractory to gemcitabine, a study published online ahead of print in the journal Annals of Oncology has shown.1

For the study, researchers sought to evaluate the efficacy and safety of adding oral leucovorin to S-1 compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer.

Researchers enrolled 142 patients and randomly assigned them 1:1 to receive S-1 40 to 60 mg orally based on body surface area plus leucovorin 25 mg orally, both twice daily for 1 week every 2 weeks, or S-1 monotherapy for 4 weeks every 6 weeks.

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Results showed that median progression-free survival was 3.8 months in the combination arm compared with 2.7 months in the S-1 monotherapy arm (HR, 0.56; 95% CI: 0.37-0.85; P=.003). Researchers found that the disease control rate was 91% and 72% in the S-1 plus leucovorin arm and the S-1 monotherapy arm, respectively (P=.004).

Overall survival was 6.3 months in the leucovorin group and 6.1 months in the S-1 alone group (HR, 0.82; 95% CI: 0.54-1.22; P=.463), but researchers found that overall survival tended to be better in the combination arm after adjusting for patient background factors (HR, 0.71; 95% CI: 0.47-1.07; P=.099).

In regard to safety, both treatments were well tolerated, but gastrointestinal toxicities were slightly more severe in the combination arm.

The investigators note that a phase 3 trial is currently underway to further evaluate S-1 plus leucovorin in a similar setting.


1. Ueno M, Okusaka T, Omuro Y, et al. A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer [published online ahead of print December 17, 2015]. Ann Oncol. doi:10.1093/annonc/mdv603.