S-1 Plus Leucovorin And Oxaliplatin May Improve Advanced Gastric Cancer Options

A 1-week on, 1-week off schedule of the oral fluoropyrimidine S-1 with leucovorin plus oxaliplatin boosts gastric cancer survival

medwireNews: S-1 plus leucovorin and oxaliplatin shows promise for the treatment of advanced cancer, suggest phase II study findings from Japan.

The oral fluoropyrimidine regimen, when given in a 1-week on, 1-week off schedule, were more effective in patients with unresectable or recurrent disease than the Japanese standard of care of S-1 plus cisplatin , say Shuichi Hironaka, from Chiba Cancer Centre in Japan, and co-workers.

They report in The Lancet Oncology that an objective response was achieved by 66% of the 47 patients given 2-week cycles of S-1 40–60 mg plus leucovorin 25 mg twice daily for 1 week with oxaliplatin 85 mg/m2 on day 1.

This compared with 43% of the 47 patients given S-1 plus leucovorin to the same schedule and 46% of the 48 patients given S-1 40–60 mg twice daily for 3 weeks plus cisplatin 60 mg/m2 on day 8 every 5 weeks.

Median progression-free survival and overall survival in the S-1 plus leucovorin and oxaliplatin group were 8.3 months and 18.4 months, respectively, compared with 4.2 and 15.6 months for patients given S-1 plus leucovorin, and 5.6 and 12.6 months for those given S-1 plus cisplatin.

Neutropenia was the most common grade 3 or 4 adverse event, affecting 26% of patients given S-1 plus leucovorin and oxaliplatin, 6% of those given S-1 plus leucovorin and 35% of the patients given S-1 plus cisplatin. Decreased appetite (30 vs 13 and 24%, respectively), anaemia (15 vs 10 and 27%) and hyponatraemia (4 vs 4 vs 18%) were also reported.
A phase III study of S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin is now underway in Japan and Korea, the authors say.

In the meantime, they note: “S-1 plus leucovorin treatment can be an alternative option for patients who are unfit for treatment with platinum-doublet chemotherapy.
“We expect that S-1 plus leucovorin will supersede S-1 monotherapy in the clinical settings where it is recognised as a standard of care, such as in adjuvant chemotherapy and maintenance therapy after discontinuing platinum.”

Tsang-Wu Liu and Li-Tzong Chen, from the National Institute of Cancer Research in Tainan, Taiwan, suggest in an accompanying comment that the 1-week on, 1-week off S-1 schedule might be better tolerated in patients of European ancestry, who are more sensitive to treatment than Japanese individuals because of genetic polymorphisms, than S-1 given on a 2–4 week on, 1-week off regimen.

However, they note that the oral fluoropyrimidine TAS-102 “might be a more attractive option for development in gastric cancer treatment in European countries”, citing its activity against fluorouracil-resistant disease and its comparable tolerability, safety and efficacy across ethnic populations.


Hironaka S, Sugimoto N, Yamaguchi K, et al. 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 2015; Advance online publication 27 November. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00410-6
Liu T-S, Chen L-T. S-1 with leucovorin for gastric cancer: how far can it go? Lancet Oncol 2015; Advance online publication 27 November. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00478-7

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