S-1 Plus Leucovorin, Oxaliplatin Active in Advanced Gastric Cancer

S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable adverse effects in patients with advanced gastric cancer, a new study published online ahead of print in the journal The Lancet Oncology.¹

Although previous research has demonstrated that leucovorin enhances the efficacy of fluorouracil in advanced gastric cancer, the antitumor activity of S-1 and leucovorin in combination with oxaliplatin in patients with advanced gastric cancer has not been studied.

Therefore, researchers sought to compare the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy.

For the multicenter, open-label, phase 2 trial, researchers enrolled 145 chemotherapy-naïve patients with unresectable or recurrent gastric cancer from 25 institutions in Japan.

Patients were randomly assigned 1:1:1 to receive S-1 40-60 mg orally plus leucovorin 25 mg orally twice daily for 1 week, every 2 weeks; S-1 plus leucovorin and oxaliplatin 85 mg/m² intravenously on day 1, every 2 weeks; or S-1 40-60 mg orally twice daily for 3 weeks plus cisplatin 60 mg/m² intravenously on day 8, every 5 weeks.

Results showed that the objective response rate was 43% (95% CI, 28.3 – 57.8) in the S-1 plus leucovorin group, 66% (95% CI, 50.7 – 79.1) in the S-1 plus leucovorin and oxaliplatin group, and 46% (95% CI, 31.4 – 60.8) in the S-1 plus cisplatin group. S-1 plus leucovorin and oxaliplatin was significantly more active than S-1 plus cisplatin (P = .063) and S-1 plus leucovorin (P = .038).

In regard to safety, the most common grade 3 to 4 adverse effects were neutropenia, decreased appetite, anemia, and hyponatremia.

A phase 3 trial evaluating S-1 plus leucovorin and oxaliplatin compared with S-1 plus cisplatin is underway.

Reference

1. 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 [published online ahead of print November 27, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00410-6.