- •Systemic chemotherapy is the standard of care for patients with unresectable advanced or metastatic pancreatic cancer.
- •The maximum tolerated dose of the SLOG regimen, S-1 plus leucovorin in combination with gemcitabine and oxaliplatin has been defined.
- •SLOG showed promising efficacies and favourable safety profiles in patients with metastatic pancreatic cancer.
- •A randomised phase II trial comparing SLOG versus modified FOLFIRINOX in advanced pancreatic cancer is ongoing.
This phase I/II study evaluated the feasibility and efficacy of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG), a triplet regimen, for treating patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Patients with chemo-naive, metastatic PDAC were eligible to receive fixed-rate infusion (10 mg/m2/min) of gemcitabine of 800 mg/m2 followed by oxaliplatin of 85 mg/m2 on day 1 plus oral S-1 and leucovorin (20 mg/m2) twice daily from days 1 to 7 in a 2-week cycle. The dose of S-1 would be escalated from 20, 30, 35 to 40 mg/m2 in a 3 + 3 designed phase I part to determine the maximum tolerated dose (MTD) for phase II study, in which the primary end-point was objective response rate (ORR). The recommended dose of S-1 was from phase I. This trial is registered at ClinicalTrials.gov: NCT01415713.
Seventy-three patients were enrolled. In the phase I study (n = 19), the MTD of S-1 was 35 mg/m2 twice daily. Of 54 patients in phase II, the ORR was 40.7% (95% confidence interval [CI], 28%–55%). The median progression-free survival and overall survival were 7.6 (95% CI, 5.6–11.0) and 11.4 (95% CI, 8.1–16.3) months, respectively. The most common grade III/IV adverse event was neutropenia (40.7%). Twenty-four percent of patients had SLOG treatment for more than 1 year. The mean relative dose intensities of gemcitabine, oxaliplatin, and S-1 were 92%, 92% and 89%, respectively.
Biweekly SLOG is a feasible regimen with promising activity and safety profiles. A randomised study comparing SLOG versus modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) in advanced PDAC is ongoing (ClinicalTrials.gov: NCT03443492).
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to European Journal of Cancer
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- SEER Cancer Statistics Factsheets: Pancreas cancer.National Cancer Institute, Bethesda, MD2019
- NCCN guidelines for treatment of cancer by site: pancreatic adenocarcinoma (version 2).National Comprehensive Cancer Network, Fort Washington2015
- Locally advanced, unresectable pancreatic cancer: American society of clinical Oncology clinical Practice guideline.J Clin Oncol. 2016; 34 (Epub 2016 May 31): 2654-2668https://doi.org/10.1200/JCO.2016.67.5561
- Cancer statistics.CA Cancer J Clin 2016. 2016; 66 (Epub 2016 Jan 7): 7-30https://doi.org/10.3322/caac.21332
- Metastatic pancreatic cancer: is there a light at the end of the tunnel?.World J Gastroenterol. 2015; 21: 4788-4801
- FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.N Engl J Med. 2011; 364: 1817-1825https://doi.org/10.1056/NEJMoa1011923
- Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with metastatic pancreatic cancer.Cancer Sci. 2014; 105: 1321-1326
- Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer.Cancer Chemother Pharmacol. 2016; 77: 595-603
- Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med. 2013; 369 (Epub 2013 Oct 16): 1691-1703https://doi.org/10.1056/NEJMoa1304369
- Phase II study of biweekly gemcitabine followed by oxaliplatin and simplified 48-h infusion of 5-fluorouracil/leucovorin (GOFL) in advanced pancreatic cancer.Cancer Chemother Pharmacol. 2009; 64: 1173-1179
- Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study.J Clin Oncol. 2013; 31 (Epub 2013 Apr 1): 1640-1648https://doi.org/10.1200/JCO.2012.43.3680
- Phase II study of oxaliplatin combined with S-1 and leucovorin (SOL) for Chinese patients with metastatic colorectal cancer.Chin J Canc. 2016; 35: 8
- 625PRandomized phase II study of S-1 plus oral leucovorin (SL) versus SL plus oxaliplatin (SOL) versus S-1 plus cisplatin (SP) in ptients with advanced gastric cancer (AGC):update overall survival data.Ann Oncol. 2014; 25: iv213-i214
- A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer.Cancer Chemother Pharmacol. 2015; 75: 569-577
- Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer.J Hepatobiliary Pancreat Sci. 2018; 25 (Epub 2018 Apr 12): 261-268https://doi.org/10.1002/jhbp.547
- 743PInitial treatment and survival in a national unselected Danish cohort of 4161 patients with pancreatic cancer.Ann Oncol. 2018; 29
- Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer.Cancer Chemother Pharmacol. 2007; 59 (Epub 2006 Jun 20): 285-293https://doi.org/10.1007/s00280-006-0265-y
- Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial.J Clin Oncol. 2010; 28 (Epub 2010 Feb 16): 1547-1553https://doi.org/10.1200/JCO.2009.25.4706
- Phase I study with pharmacokinetics of S-1 on an oral daily schedule for 28 days in patients with solid tumors.Clin Cancer Res. 2003; 9: 134-142
- Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors.J Clin Oncol. 2000; 18: 2772-2779https://doi.org/10.1200/JCO.2000.18.14.772
- Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma.J Clin Oncol. 2005; 23 (Epub Sep. 6): 6957-6965https://doi.org/10.1200/JCO.2005.01.917
- Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer.Cancer Chemother Pharmacol. 2017; 79 (Epub 2016 Dec 8): 107-116https://doi.org/10.1007/s00280-016-3212-6
- Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest.Mol Clin Oncol. 2015; 3 (Epub Feb 2): 527-532https://doi.org/10.3892/mco.2015.500
- S-1 plus leucovorin versus S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer: a randomised, multicentre, open-label, phase 2 trial.Lancet Oncol. 2016; 17 (Epub 2015 Nov 28): 99-108https://doi.org/10.1016/S470-2045(15)00410-6
- S-1 with leucovorin for gastric cancer: how far can it go?.Lancet Oncol. 2016; 17 (Epub 2015 Nov 28): 12-14https://doi.org/10.1016/S470-2045(15)00478-7
Published online: November 22, 2019
Accepted: October 24, 2019
Received in revised form: October 12, 2019
Received: May 18, 2019
© 2019 Elsevier Ltd. All rights reserved.