Our previous studies showed a triplet GOFL regimen consisting of gemcitabine plus modified FOLFOX4 was well-tolerated and moderate active in advanced PDAC, and the feasibility of replacing infusion 5-FU/LV with oral S-1/LV, the SLOG regimen, in a dose-escalating, phase I study. Herein, we report the phase II results of the SLOG in mPDAC patients.
Patients with chemo-naïve mPDAC, ECOG PS 0-1, and 20-75 y/o of age were eligible. Intravenous fixed-rate infusion of 800 mg/m2 gemcitabine followed by 2-hr infusion of 85mg/m2 oxaliplatin on D1 plus oral S-1/LV 35/20 mg/m2, twice daily, D1-D7 were given Q 14 days as a cycle. The primary endpoint was objective response rate (ORR). Simon’s optimal two-stage design was used with estimated p0=25% and p1=40%.
Between Jun. 2013 and Oct. 2015, a total of 54 patients were included, with median age of 59 y/o, ECOG PS = 1 in 82%, and the presence of liver metastases in 66.7%. At the cut-off Feb.01, 2017, nine patients remained alive and their median follow-up time was 21.3 months. The ORR was partial response in 22 patients (ORR=40.7%, 95% CI, 28-55%) and stable diseases in 19 patients (35.2%). Long-term disease control rate (stable disease >16 weeks) was 64.8% (95% CI, 51-77%). The median progression-free survival and overall survival was 7.6 (95% CI, 4.4-10.7) and 11.4 (95% CI, 8.1-16.3) months, respectively. One-year and two-year survival rates were 46% and 17%, respectively. The most common treatment-related grade 3-4 adverse events included neutropenia (40.7%), anorexia (14.8%), nausea (11.1%), thrombocytopenia (9.3%), and diarrhea (7.4%).
Current study demonstrated SLOG is a highly active regimen with manageable and favorable safety profiles for mPDAC patients. A randomized phase II trial comparing SLOG vs. modified FOLFIRINOX in advanced PDAC patients is ongoing.
Clinical trial identification
Legal entity responsible for the study
Taiwan Cooperative Oncology Group, National Health Research Institutes.
National Health Research Institutes.
We thank the Clinical Trial Information Management System (CTIMeS) at NHRI for the data collection. Free drug sponsors for this study: oxalip, oral leucovorin and S-1 (tegafur/gimeracil/oteracil potassium) from TTY Biopharm Co., Ltd., Taipei, Taiwan; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan.
J-S. Chen: Honoraria: Ono, Eli Lilly, MSD, TTY, Novartis. Y-S. Shan: Honoraria: TTY, PharmaEngine. L-T. Chen: Research funding: Novartis, Merck Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; Honoraria: Ono, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; Patents & royalties: ENO-1 mAb/HuniLife; Membership on any entity’s Board of directors or advisory committees: PharmaEngine. All other authors have declared no conflicts of interest.